The Scientific Difference Between Standard Synthetic Melatonin & Natural Plant-Based Melatonin

Are natural source nutraceuticals better than the synthetic version? The honest answer is sometimes yes, sometimes no. It really depends on whether the science on that nutraceutical is able to show a demonstrable difference. For most of the time melatonin has been on the market there has really been no opportunity to answer this question since synthetic melatonin was the exclusive source of this nutraceutical. This has changed, however, since the introduction of Somnatural?, a natural phytomelatonin.

Somnatural? phytomelatonin

Somnatural? phytomelatonin is natural, plant-based, Vegan Certified, Non-GMO Project Verified, kosher, and halal, which has broad appeal. In addition, laboratory analysis of Somnatural? reveals that in addition to its natural phytomelatonin content, it also contains 2-hydroxymelatonin and N-acetylserotonin.

The significance of this is that 2-hydroxymelatonin has greater immune benefits than melatonin[1]—and 2-hydroxymelatonin also has been shown to promote resistance to physical stresses in plants[2] and provide antioxidant activity against oxidative stress[3]. Likewise, research[4] has shown that N-acetylserotonin may play an important role in mood regulation, as well as stimulate proliferation of neuroprogenitor cells (i.e., cells that give rise to many different nerve cells) and prevent some of the negative effects of sleep deprivation. It may also turn out to play a role in mitigating common, age-related cognitive decline[5].

Furthermore, unlike synthetic melatonin, none of the following chemical agents are used in its production: diethylmaonate, acrylonitrile, potassium hydroxide, p-methoxyanilin, methanol, sodium hydroxide, acetic anhydride, and others. But even more meaningful, phytomelatonin actually has some biological advantages over synthetic melatonin. Before sharing that information, let’s do a quick review of the functions of melatonin.

About melatonin

Melatonin is a hormone with a wide array of biological activities in plants, animals, unicellular organisms, and fungi. In humans and other mammals, it is produced by the tiny pineal gland, located behind the third ventricle of the brain. Melatonin plays important regulatory roles in sleep, body temperature balance, locomotory activities, circadian rhythms, immune system, and retinal physiology[6] [7].

Melatonin supplementation is best known for its role in helping people fall asleep[8].?In adults with difficulty sleeping, short-term use of melatonin modestly reduces the time it takes to fall asleep (sleep latency).[9] In addition, some patients report minor improvement in subjective feelings of sleep quality.[10] [11] [12]?Furthermore, research has shown that melatonin supplementation is effective in adults with difficulty sleeping, secondary to other causes.[13]

In addition, both human and laboratory research has shown that melatonin decreases the upregulation of or suppresses levels of inflammatory chemicals in the body[14] [15] [16] [17] [18] [19] [20] [21]. Interestingly, this additional benefit also has a relationship to sleep.

Inflammation and sleep

Poor sleep is associated with higher levels of inflammatory markers. One study[22] found that a significant association between the sleep inconsistency and inflammation (p?= 0.021), suggesting inconsistent sleep is associated with higher levels of inflammatory biomarkers. Another study[23] found that self-reported insomnia symptoms were associated with higher values of inflammatory markers, while higher amounts of rapid eye movement (REM) sleep were associated with lower inflammatory markers. Sleep disturbances, specifically difficulties maintaining sleep and early morning awakenings were associated with higher inflammatory markers.

About phytomelatonin

As with animals, melatonin is also produced in all plant species. In this case it is called phytomelatonin, and it aids plants in terms of root growth, leaf morphology, chlorophyll preservation and fruit development.[24] So how does phytomelatonin compare to synthetic melatonin?

To begin with, the scope of the impact of phytomelatonin in humans is broad, with roles having been demonstrated in mood swings, body temperature, sleep, cardiac rhythms, and immunological regulation modulators, as well as antioxidant property.[25]

An in-vitro study[26] was conducted, comparing the effects of phytomelatonin and synthetic melatonin, with or without vitamin C, in HaCaT keratinocytes (i.e., a type of skin cell) using a COX-2 enzyme inhibitory test (COX-2 is an inflammatory marker). Results were that COX-2 inhibitory activity was found to be about 6.5 times stronger with phytomelatonin than with synthetic melatonin. The reason for this is unknown but may be associated with other naturally occurring compounds in phytomelatonin.

In any case, additional research has also shown that phytomelatonin is capable of decreasing plasma levels of other inflammatory makers, including interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a), and C-reactive protein (CRP), heat shock protein 70 extracellular (Hsp70e), and vascular endothelial growth factor (VEGF)[27].

It is also worth noting that, in animal research[28], phytomelatonin was shown to have impressive bioavailability. Furthermore, the elevated level of melatonin in the blood was associated with a rise in total antioxidant capacity of the blood with an ability to resist free radical damage.

Conclusion

Since phytomelatonin is predominantly melatonin, it has the capacity to provide substantial support for the sleep cycle. However, since phytomelatonin was shown to have 6.5 times stronger anti-inflammatory activity (as previously described), and since inflammation is known to play a significant role in poor sleep, the use of natural phytomelatonin as an alternative to synthetic melatonin may provide an additional positive impact on the sleep cycle. Furthermore, the marketing advantage of a natural, plant-based, Vegan Certified, Non-GMO Project Verified, kosher, and halal Somnatural? phytomelatonin is certainly likely to have appeal over synthetic melatonin that is manufactured using a range of chemical agents.

Nutraland USA offers clean, plant-based and sustainable branded ingredients supported by science. Our nutraceuticals are good for you, and good for the planet. For more information about how you can use Somnatural? phytomelatonin in your dietary supplements, contact [email protected]; 949-988-7615.

References

[1] Yang Y, Zhou R, Park SY, Back K, Bae WK, Kim KK, Kim H. 2-Hydroxymelatonin, a Predominant Hydroxylated Melatonin Metabolite in Plants, Shows Antitumor Activity against Human Colorectal Cancer Cells. Molecules. 2017 Mar 14;22(3):453.

[2] Hy-Jung L, Kyoungwhan B. 2-Hydroxymelatonin promotes the resistance of rice plant to multiple simultaneous abiotic stresses (combined cold and drought). J Pineal Res. 2016; 61(3):303-16.

[3] Pérez-González A, Galano A, Alvarez-Idaboy JR, Tan DX, Reiter RJ. Radical-trapping and preventive antioxidant effects of 2-hydroxymelatonin and 4-hydroxymelatonin: Contributions to the melatonin protection against oxidative stress. Biochim Biophys Acta Gen Subj. 2017 Sep;1861(9):2206-2217.

[4] Tosini G, Ye K, Iuvone PM. N-acetylserotonin: neuroprotection, neurogenesis, and the sleepy brain. Neuroscientist. 2012 Dec;18(6):645-53..

[5] Oxenkrug G, Ratner R. N-acetylserotonin and aging-associated cognitive impairment and depression. Aging and Disease. 2012; 3(4):330-8.

[6] Carrillo-Vico A, Lardone PJ, Alvarez-?nchez N, et al. Melatonin: buffering the immune system. Int J Mol Sci. 2013;14: 8638e83.

[7] Paredes SD, Korkmaz A, Manchester LC, Tan DX, Reiter RJ. Phytomelatonin: a review. J Exp Bot. 2009; 60:57e69

[8] Buscemi N, Vandermeer B, Hooton N, et al. The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J Gen Intern Med 2005;20:1151-8.

[9] Buscemi N, Vandermeer B, Hooton N, et al. The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J Gen Intern Med 2005;20:1151-8.

[10] Ellis CM, Lemmens G, Parkes JD. Melatonin and insomnia. J Sleep Res 1996;5:61-5.

[11] James SP, Sack DA, Rosenthal NE, Mendelson WB. Melatonin administration in insomnia. Neuropsychopharmacol 1990;3:19-23.

[12] Buscemi N, Vandermeer B, Pandya R, et al. Melatonin for treatment of sleep disorders. Summary, Evidence Report/Technology Assessment #108. (Prepared by the Univ of Alberta Evidence-based Practice Center, under Contract#290-02-0023.) AHRQ Publ #05-E002-2. Rockville, MD: Agency for Healthcare Research & Quality. November 2004.

[13] Buscemi N, Vandermeer B, Hooton N, et al. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ 2006;332:385-93.

[14] Reiter, R. J., Calvo, J. R., Karbownik, M., Qi, W., and Tan, D. X. Melatonin and its relation to the immune system and inflammation. Ann N.Y.Acad Sci 2000;917:376-386.

[15] Lahiri, S., Singh, P., Singh, S., Rasheed, N., Palit, G., and Pant, K. K. Melatonin protects against experimental reflux esophagitis. J.Pineal Res. 2009;46(2):207-213.?

[16] Makay, B., Makay, O., Yenisey, C., Icoz, G., Ozgen, G., Unsal, E., Akyildiz, M., and Yetkin, E. The interaction of oxidative stress response with cytokines in the thyrotoxic rat: is there a link? Mediators.Inflamm. 2009;2009:391682.?

[17] Tahan, V., Atug, O., Akin, H., Eren, F., Tahan, G., Tarcin, O., Uzun, H., Ozdogan, O., Tarcin, O., Imeryuz, N., Ozguner, F., Celikel, C., Avsar, E., and Tozun, N. Melatonin ameliorates methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in rats. J.Pineal Res. 2009;46(4):401-407.

[18] Kim, T. H., Jung, J. A., Kim, G. D., Jang, A. H., Ahn, H. J., Park, Y. S., and Park, C. S. Melatonin inhibits the development of 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions in NC/Nga mice. J.Pineal Res. 2009;47(4):324-329.?

[19] Yang, F. L., Subeq, Y. M., Lee, C. J., Lee, R. P., Peng, T. C., and Hsu, B. G. Melatonin ameliorates hemorrhagic shock-induced organ damage in rats. J.Surg.Res. 5-15-2011;167(2):e315-e321.

[20] Fang, Q., Chen, G., Zhu, W., Dong, W., and Wang, Z. Influence of melatonin on cerebrovascular proinflammatory mediators expression and oxidative stress following subarachnoid hemorrhage in rabbits. Mediators.Inflamm. 2009;426346.?

[21] Cichoz-Lach, H., Celinski, K., Konturek, P. C., Konturek, S. J., and Slomka, M. The effects of L-tryptophan and melatonin on selected biochemical parameters in patients with steatohepatitis. J.Physiol Pharmacol. 2010;61(5):577-580.?

[22] Dzierzewski JM, Donovan EK, Kay DB, Sannes TS, Bradbrook KE. Sleep Inconsistency and Markers of Inflammation. Front Neurol. 2020 Sep 16;11:1042.

[23] Ghilotti F, Bellocco R, Trolle Lagerros Y, Thorson A, Theorell-Hagl?w J, ?kerstedt T, Lindberg E. Relationship between sleep characteristics and markers of inflammation in Swedish women from the general population. J Sleep Res. 2021 Apr;30(2):e13093.

[24] Reiter RJ, Tan DX, Zhou Z, Cruz MH, Fuentes-Broto L, Galano A. Phytomelatonin: assisting plants to survive and thrive. Molecules. 2015 Apr 22;20(4):7396-437.

[25] Arnao MB, Hern_andez-Ruiz J. The potential of phytomelatonin as a nutraceutical. Molecules 2018;23:1e19

[26] Kukula-Koch W, Szwajgier D, Gawe?-B?ben K, Strz?pek-Gomó?ka M, G?owniak K, Meissner HO. Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties. Molecules. 2021 Oct 8;26(19):6087.

[27] Al-Rasheed NM, Fadda L, Attia HA, Sharaf IA, Mohamed AM, Al-Rasheed NM. Pulmonary prophylactic impact of melatonin and/or quercetin: a novel therapy for inflammatory hypoxic stress in rats. Acta Pharm. 2017;67:125e35.

[28] Reiter RJ, Tan DX, Manchester LC, Simopoulos AP, Maldonado MD, Flores LJ, Terron MP. Melatonin in edible plants (phytomelatonin): Identification, concentrations, bioavailability and proposed functions. World Rev Nutr Diet. 2007;97:211-230.?