Epithalon

Potential Benefits of Epithalon

• Reverses signs of aging [1-16]
• Prevents and treats cancer [12 ,17-22]
• Prevents cardiovascular disease [23-26]
• Boosts brain health [9, 27-29]
• Promotes quality sleep [5, 7, 30-32]
• Improves eye health [33-37]
• Boosts immunity [11, 38-41]
• Treats symptoms of diabetes [42-45]

What is Epithalon?

Epithalon (Epitalon) is a synthetic peptide that reproduces the effects of epithalamin, a polypeptide found in the pineal gland. Its main role is to increase the natural production of telomeres. This allows DNA replication that is important for the formation and regeneration of cells.

How Epithalon Works?

Epithalon increases the body’s natural production of telomerase, an enzyme that helps cells produce telomeres. These act as cap protectors of our DNA that become worn out during DNA replication. The replication process is essential for cell division during the growth or repair of damaged tissues in the body. [1] Similar to other bodily functions, telomeres length shortens as we age. [2] Progressive shortening of telomeres may affect the health and lifespan of an individual. The good news is that we can preserve these telomeres, and there are scientific discoveries that can elongate them. In theory, an elongated telomere can extend the lifespan of a copy of DNA and allows it to be more efficient with cell replication.

Chemical Structure of Epithalon

Research on Epithalon

Reverses Signs of Aging

Compelling evidence suggests that the administration of epithalon can increase life span and reverse signs of aging:

1. It was concluded that the administration of the synthetic peptide epithalon might overcome genetic limitations and normalize body functions. [1]
2. Epithalon has been found to fight signs of aging through its immunomodulatory properties, an integral function of the immune system. [2]
3. A study was made on rats that showed epithalon administration resulted in increased melatonin production, improved immunological parameters, enhanced antioxidant defenses, and restoration of reproductive function. [3]
4. Circadian rhythms of melatonin and cortisol production in old rhesus monkeys were also restored. [4]
5. Epithalon was found to stimulate the release of melatonin in older people, which resulted in a deeper sleep. [5]
6. It also showed to improve complications with Alzheimer’s disease, amyotrophic lateral sclerosis, jet lag, and nocturnal hypertension. [6]
7. In aging monkeys, epithalon stimulated evening melatonin secretion and reestablished the circadian rhythm associated with cortisol release. [7]
8. Common fruit flies exposed to epithalon during their developmental stage showed an increased lifespan from 11-16%. [8]
9. Epithalon showed a substantial decrease in the extent of memory disorders in old rats. [9]
10. There is a study done on chicks that suggest that epithalamin stimulates the growth of brain and spinal nerves. [10]
11. Epithalon has been shown to promote an increase in lymphocytes from the thymus of elderly people, thus improving immune function in the specific age group. [11]
12. In female mice, epithalon improved biomarkers of aging and life span. [12-13]
13. Epithalon was found to have more benefits than melatonin as it also stimulates superoxide dismutase (SOD), ceruplasmin, and other antioxidant enzymes. [14]
14. In male rats, epithalamin increased total antioxidant capacity by 36% and superoxide dismutase (a powerful antioxidant) by 19%. [15]
15. Because of its ability to stimulate melatonin production and mechanisms related to melatonin, epithalon’s antioxidant benefits were also proven. [16]

Prevents and Treats Cancer

One of the diseases caused by oxidative stress or free radical damage is cancer. Studies suggest that epithalon’s ability to increase the body’s antioxidant capacity can also help with slowing cancer growth:

1. In female spontaneously hypertensive rats (SHR), epithalon injection inhibited the development of leukemia. [12]
2. In female transgenic mice, epithalon administration inhibited the development of breast cancer. [17]
3. In rats, continued epithalon administration throughout the experiment resulted in a significant inhibitory effect against colon cancer. [18]
4. In mice, epithalon slowed and inhibited the spread of tumors. [19]
5. When epithalon was given to rats with colon cancer, the peptide increased lymph flow (containing white blood cells) and apoptosis (programmed cell death), while it slowed cancer growth. [20]
6. In mice with mammary tumors, epithalon significantly decreased the number of mice with multiple tumors and decreased the maximum size of tumors compared to control mice. [21]
7. A study in mice found that treatment with epithalon reduced the number of mice with malignant tumors (cancerous tumors) and prevented cancer from metastasizing (moving to another location in the body) in all of the treated mice. [22]

Prevents Cardiovascular Disease

Studies suggest that epithalon can help reduce the risk of heart disease by improving various health parameters:

1. A study showed that the ability of epithalon to preserve telomere length can help prevent cardiovascular disease. [23]
2. In middle-aged and elderly women, epithalon supplementation greatly reduced the occurrence of ischemic heart disease. [24]
3. A study showed that elder women treated with epithalamin had improved lipid metabolism, which eventually led to a reduction in arterial blood pressure. [25]
4. Epithalamin was also shown to improve functional stability and quality of cardiovascular system regulation, showing improvement in blood flow of the patients treated. [26]

Boosts Brain Health

Evidence also suggests that epithalon is integral for maintaining normal cognitive function:

1. Epithalon showed a substantial decrease in the extent of memory disorders in old rats. [9]
2. A study showed that epithalon plays a role in the formation of new neurons in the brain. [27]
3. In rats, intranasal administration of epithalon resulted in significant activation of neuronal activities. [28]
4. In male rats, intranasal administration of epithalon triggered the neurons to become more active. [29]

Promotes Quality Sleep

Studies suggest that the ability of epithalon to regulate the production of the sleep hormone melatonin can help promote quality sleep:

1. In older people, epithalon was found to stimulate the release of melatonin, which resulted in a deeper sleep. [5]
2. In old female monkeys, epithalon greatly stimulated melatonin synthesis which is important for good sleep. [7]
3. In old monkeys, epithalon treatment was found to be effective in treating age-related hormonal imbalance by inducing increased melatonin production. [30]
4. In old monkeys and elderly people, epithalon induced safe regulation of blood melatonin levels without any side effects. [31]
5. In healthy elderly patients, epithalon treatment initiated the melatonin-producing function of the pineal gland which in turn improved sleep quality. [32]

Improves Eye Health

Evidence also found that epithalon can help combat age-related decline in eye function and other eye disorders:

1. In rats, epithalon administration resulted in improved retinal functionality and preserved its structure. [33-35]
2. A study showed that epithalon stimulated the proliferation of retinal and pigmented epithelial cells. [36]
3. In patients with degenerative retinal lesions, epithalon therapy produced beneficial effects on visual function. [37]

Boosts Immunity

Studies also show that epithalon has immune-boosting properties:

1. In aging mice, it was shown that epithalon could increase T-cell production. [11]
2. In chickens, epithalon injections effectively treated humoral immune deficiency. [38-39]
3. In adult and old mice, epithalon administration increased the levels of immune system cells such as CD3+, CD4+CD8-, CD4-CD8+, and Mac-1(+)-. [40]
4. In old rats, epithalon played a role in regulating immunity by maintaining optimal spleen function. [41]

Treats Symptoms of Diabetes

There are also studies supporting the beneficial effects of epithalon on blood sugar and diabetic symptoms:

1. In female rhesus monkeys of various ages, epithalon restored the insulin level in response to a glucose load. [42]
2. In non-insulin-dependent (Type 2) diabetics, epithalamin treatment improved carbohydrate metabolism and insulin sensitivity. [43]
3. Diabetic retinopathy (eye complication of diabetes) was also improved with epithalon administration in diabetic patients. [44]
4. In young and old rats, epithalon increased protein and sugar digestion. [45]

Associated Side Effects of Epithalon

Epithalon side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on epithalon. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of epithalon. Despite this, it was listed as a side effect associated with epithalon even though these associated side effects are very uncommon.

Side effects associated with epithalon may include the following:

• Diarrhea
• Difficulty sleeping
• Fatigue
• Flu-like symptoms
• Headache
• Irregular heartbeat
• Joint pain
• Nausea

References

1. Vladimir Kh Khavinson. Peptides and Ageing. Neuro Endocrinol Lett 2002;23 Suppl 3:11-144.
2. M Karasek. Melatonin, human aging, and age-related diseases. Exp Gerontol Nov-Dec 2004;39(11-12):1723-9. doi: 10.1016/j.exger.2004.04.012.
3. V M Dilman, V N Anisimov, M N Ostroumova, V K Khavinson, V G Morozov. Increase in lifespan of rats following polypeptide pineal extract treatment. Exp Pathol (Jena) 1979;17(9):539-45. doi: 10.1016/s0014-4908(79)80076-9.
4. I F Labunets, G M Butenko, L V Magdich, O V Korkushko, V Kh Khavinson, V B Shatilo. Effect of epithalamin on circadian relationship between the endocrine function of the thymus and melatonin-producing function of the pineal gland in elderly people. Bull Exp Biol Med 2004 May;137(5):507-9. doi: 10.1023/b:bebm.0000038165.09563.b5.
5. S V Trofimova, N S Linkova, A A Klimenko, T V Kvetnaia, V Kh Khavinson. Pineamin increased pineal melatonin synthesis in elderly people. Adv Gerontol 2017;30(3):422-426.
6. Available from https://nccih.nih.gov/health/melatonin#hed3.
7. V Khavinson,, N Goncharova, B Lapin. Synthetic tetrapeptide epitalon restores disturbed neuroendocrine regulation in senescent monkeys. Neuro Endocrinol Lett 2001 Aug;22(4):251-4.
8. V K Khavinson, D M Izmaylov, L K Obukhova, V V Effect of epitalon on the lifespan increase in Drosophila melanogaster. Mech Ageing Dev 2000 Dec 1;120(1-3):141-9.
9. I A Vinogradova. Comparative study of the effects of melatonin and epitalon on the protracted memory under the shuttle labyrinth test conditions in rats in the course of aging. Eksp Klin Farmakol Nov-Dec 2006;69(6):13-6.
10. N I Chalisova, V K Khavinson. Studies of cytokines in nerve tissue cultures. NeurosciBehavPhysiol May-Jun 2000;30(3):261-5. doi: 10.1007/BF02471779.
11. N S Lin’kova, B I Kuznik, V Kh Khavinson. Peptide Ala-Glu-Asp-Gly and interferon gamma: their role in immune response during aging. Adv Gerontol 2012;25(3):478-82.
12. Anisimov VN, Khavinson VKh, Popovich IG, Zabezhinski MA, Alimova IN, Rosenfeld SV, Zavarzina NY, Semenchenko AV, Yashin AI. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology. 2003;4(4):193-202. doi: 10.1023/a:1025114230714. PMID: 14501183.
13. Anisimov VN, Khavinson VKh, Alimova IN, Semchenko AV, Yashin AI. Epithalon decelerates aging and suppresses development of breast adenocarcinomas in transgenic her-2/neu mice. Bull Exp Biol Med. 2002 Aug;134(2):187-90. doi: 10.1023/a:1021104819170. PMID: 12459848.
14. Syed Saqib Ali, Haseeb Ahsan, Mohammad Khalid Zia, Tooba Siddiqui, Fahim Halim Khan. Understanding oxidants and antioxidants: Classical team with new players. J Food Biochem2020 Mar;44(3):e13145. doi: 10.1111/jfbc.13145. Epub 2020 Jan 20.
15. L S Kozina, A V Arutjunyan, V KhKhavinson. Antioxidant properties of geroprotective peptides of the pineal gland. Arch GerontolGeriatr. 2007;44 Suppl 1:213-6. doi: 10.1016/j.archger.2007.01.029.
16. V N Anisimov, A V Arutjunyan, V K Khavinson. Effects of pineal peptide preparation Epithalamin on free-radical processes in humans and animals. Neuro Endocrinol Lett 2001;22(1):9-18.
17. 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.
18. Kossoy G, Zandbank J, Tendler E, Anisimov V, Khavinson V, Popovich I, Zabezhinski M, Zusman I, Ben-Hur H. Epitalon and colon carcinogenesis in rats: proliferative activity and apoptosis in colon tumors and mucosa. Int J Mol Med. 2003 Oct;12(4):473-7. PMID: 12964022.
19. 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.
20. E EVishnevskaia, I A Kosenko. Long-term results of comprehensive treatment for cervical cancer with poor prognosis. VoprOnkol1999;45(4):420-3.
21. Vladimir N Anisimov. The role of pineal gland in breast cancer development. Crit Rev Oncol Hematol2003 Jun;46(3):221-34. doi: 10.1016/s1040-8428(03)00021-0.
22. Khavinson VKh, Morozov VG. Geroprotektornaia éffektivnost’ timalina i épitalamina [Geroprotective effect of thymalin and epithalamin]. Adv Gerontol. 2002;10:74-84. Russian. PMID: 12577695.
23. Zhan Y, Hägg S. Telomere length and cardiovascular disease risk. Curr Opin Cardiol. 2019 May;34(3):270-274. doi: 10.1097/HCO.0000000000000613. PMID: 30747731.
24. G A Merkur’eva, G A Ryzhak. Effect of the pineal gland peptide preparation on the diurnal profile of arterial pressure in middle-aged and elderly women with ischemic heart disease and arterial hypertension. Adv Gerontol2008;21(1):132-42.
25. V A Cherkashin, G F Semin, A AVeretenko. Optimization of cardiovascular function by peptide bio-regulators. Klin Med Mosk2002;80(5):30-4.
26. O V Korkushko, V KhKhavinson, V B Shatilo, I A Antonyuk-Shcheglova. Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging. Bull Exp Biol Med 2006 Sep;142(3):356-9. doi: 10.1007/s10517-006-0365-z.
27. Khavinson V, Diomede F, Mironova E, et al. AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Possible Epigenetic Mechanism. Molecules. 2020;25(3):609. Published 2020 Jan 30. doi:10.3390/molecules25030609.
28. 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.
29. Sibarov DA, Vol’nova AB, Frolov DS, Nosdrachev AD. [Intranasal epitalon infusion modulates neuronal activity in the rat neocortex]. Ross Fiziol Zh Im I M Sechenova. 2006 Aug;92(8):949-56. Russian. PMID: 17217245.
30. Goncharova ND, Vengerin AA, Shmaliĭ AV, Khavinson VKh. Peptidnaia korrektsiia vozrastnykh narusheniĭ funktsii épifiza u obez’ian [Peptide correction of age-related pineal disturbances in monkeys]. Adv Gerontol. 2003;12:121-7. Russian. PMID: 14743609.
31. 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.
32. 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.
33. Khavinson V, Razumovsky M, Trofimova S, Grigorian R, Razumovskaya A. Pineal-regulating tetrapeptide epitalon improves eye retina condition in retinitis pigmentosa. Neuro Endocrinol Lett. 2002 Aug;23(4):365-8. PMID: 12195242.
34. Khavinson VKh, Razumovsky MI, Trofimova SV, Razumovskaya AM. Retinoprotective effect of Epithalon in campbell rats of various ages. Bull Exp Biol Med. 2003 May;135(5):495-8. doi: 10.1023/a:1024931812822. PMID: 12910293.
35. Khavinson VKh, Razumovskii MI, Trofimova SV, Grigor’yan RA, Chaban TV, Oleinik TL, Razumovskaya AM. Effect of epithalon on age-specific changes in the retina in rats with hereditary pigmentary dystrophy. Bull Exp Biol Med. 2002 Jan;133(1):87-9. doi: 10.1023/a:1015125031829. PMID: 12170316.
36. Khavinson VKh, Zemchikhina VN, Trofimova SV, Malinin VV. Effects of peptides on proliferative activity of retinal and pigmented epithelial cells. Bull Exp Biol Med. 2003 Jun;135(6):597-9. doi: 10.1023/a:1025497806636. PMID: 12937684.
37. Available at https://www.researchgate.net/publication/11193495_Pineal-regulating_tetrapeptide_epitalon_improves_eye_retina_condition_in_retinitis_pigmentosa.
38. Kuznik BI, Pateiuk AV, Baranchugova LM, Rusaeva NS. [Effects of epithalon and cortagene on immunity and hemostasis in neonatallyhypophysectomized chicken and old birds]. Adv Gerontol. 2008;21(3):372-81. Russian. PMID: 19432169.
39. Kuznik BI, Pateiuk AV, KhavinsonVKh, Malinin VV. Vliianieépitalonanaimmunitetigemostaz u gipofizéktomocheskikhtsypliatistarykhkur [Effect of epitalon on the immunity and hemostasis in hypophysectomized chicken and old hens]. Adv Gerontol. 2004;13:90-3. Russian. PMID: 15490730.
40. Labunets IF, Butenko GM, KhavinsonVKh, Magdich LV, Dragunova VA, Pishel’ IN, Azarskova MV. Reguliruiushcheevliianiepeptidovépifizanarazvitie T-limfotsitov u mysheĭlinii CBA pristarenii: rol’ mikrookruzheniiaorganovimmunnoĭsistemyineĭroéndokrinnykhfaktorov [Regulating effect of pineal gland peptides on development of T-lymphocytes in CBA aging mice: role of microenvironment of immune system organs and neuroendocrine factors]. Adv Gerontol. 2003;12:111-20. Russian. PMID: 14743608.
41. Khavinson VK, Konovalov SS, Yuzhakov VV, Popuchiev VV, Kvetnoi IM. Modulating effects of epithalamin and epithalon on the functional morphology of the spleen in old pinealectomized rats. Bull Exp Biol Med. 2001 Nov;132(5):1116-20. doi: 10.1023/a:1017989113287. PMID: 11865335.
42. N D Goncharova, AAVengerin, V KhKhavinson, B A Lapin. Peptide correction of age-related hormonal dysfunction of the pancreas in monkeys. Bull Exp Biol Med 2004 Jul;138(1):80-3. doi: 10.1023/b:bebm.0000046946.25425.f5.
43. S B Shustov, V KhKhavinson, T S Shutak, B V Romashevskiĭ. Epithalamin effects on carbohydrate metabolism and cardiovascular system in patients with non-insulin dependent diabetes mellitus. Klin Med Mosk1998;76(9):45-8.
44. Vladimir KhKhavinson, Vyacheslav G Morozov. Peptides of pineal gland and thymus prolong human life. NeuroEndocrinolLett Jun-Aug 2003;24(3-4):233-40.
45. V KhKhavinson, V VMalinin, N M Timofeeva, V VEgorova, AANikitina. Effects of epithalon on activities gastrointestinal enzymes in young and old rats. Bull Exp Biol Med 2002 Mar;133(3):290-2. doi: 10.1023/a:1015807305791.