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One of the interesting benefits of phytomelatonin over an isolated, synthesized chemical compound of melatonin is the complex, diverse composition of phytochemicals in the plant matrix concentrate. For example, it contains small amounts of the xanthophyll carotenoids, lutein, and zeaxanthin, which are known to concentrate in the back of the eye, specifically in the macula and fovea (3). Research suggests that these plant compounds may help protect the eyes by absorbing harmful blue light (3,4). Therefore, not only does phytomelatonin supply the bio-identical melatonin to help with circadian rhythm imbalance at night, but it also adds to the photoprotective compounds for the eye to shield against blue light, making for a complete multi-functional approach.


In fact, those additional constituents may completely or partially explain why this phytomelatonin outperformed synthetic melatonin in cellular assays for inflammation (using COX-2 inhibition) and free radical scavenging (1) (see Table 1).


Table 1: Comparison between phytomelatonin and synthetic melatonin.

Melatonin Review Paper_Phytomelatonin.png

With the increased need for melatonin and safe, yet environmentally friendly formats, various manufacturers have investigated alternatives (1,2). Although more research is needed comparing synthetic and plant-based sources of melatonin, there is some initial indication that phytomelatonin may have advantages related to improved bioavailability and efficacy. One of the unique features of phytomelatonin is that it occurs in a complex with other adjunctive plant constituents. A particular proprietary form of phytomelatonin made from alfalfa (Medicago sativa), chlorella powder (Chlorella vulgaris), and rice (Oryza sativa) powders have been shown to contain other phytonutrients in addition to phytomelatonin such as chlorophyll, beta-carotene, isoflavones, phytates, and saponins, all of which are naturally occurring in the plant matrix concentrate (1) (see Figure 1).

Synthetic Melatonin
Customized cultivation technique of selecting the ideal location, soil, climate and optimal method/time to harvest based on the plant’s cycles to optimize melatonin levels
Chemical synthesis
Bioidentical melatonin plus other plant actives; no excipients, fillers, or binding agents
Bioidentical melatonin and possibly contaminants from the chemical synthesis; depending on the dietary supplement, it may contain excipients, fillers, or binding agents
Environmentally safe?
No, uses toxic solvents and generates pollution.
Other nutritionally active compounds included
(Essential) Fatty acids, amino acids, vitamins (vitamin K, riboflavin (vitamin B2), choline, vitamin E, thiamin (vitamin B1), pyridoxine (vitamin B6), biotin), minerals (trace amounts of calcium, magnesium, zinc, iron, manganese, selenium, copper, potassium, sodium, phosphorus, chloride, iodine), phytonutrients (beta-carotene, xanthophyll, zeaxanthin, lutein, chlorophyll, violaxanthin); Concentration of these adjunctive compounds depend on growing and seasonal changes.
Anti-inflammatory activity
Yes, more effective in inhibiting COX-2 in a cellular assay compared with synthetic melatonin (1). (Figure 1)
Yes, although not more effective than phytomelatonin* (1).
Antiradical scavenging activity
Yes, it possesses significantly stronger free radical scavenging capacity as compared to synthetic melatonin using a cellular assay to assess Free Radical Scavenging Percentage (DPPH%) (1). (Figure 2)
Yes, it has antiradical scavenging activity, although less than phytomelatonin * (1).
Oxygen Radical Absorbance Capacity (ORAC)
17,200–18,500 (5) (Figure 4)
1932, 4492 (6) 4830 (7) (Figure 4)

Figure 1: Nutritional characteristics of phytomelatonin. The phytomelatonin detailed below refers to the proprietary format utilized in [35]. Graphic created using using images from pavelnaumov (chlorella, alfalfa), Victoria Sergeeva (rice), and Walrus_d’s (melatonin). accessed July 27, 2022.

Kukula-Koch et al. (1) performed cellular assays to determine if superior effects in anti-radical, antioxidant, and anti-inflammatory activities exist in phytomelatonin compared to the synthetic form. Based on these in vitro results using human cell lines, they reported significant benefits with phytomelatonin compared to synthetic melatonin (1). Phytomelatonin was found to have 646% stronger COX-2 inhibition (see Figure 1), 267–470% more potent free-radical scavenging ability (see Figure 2), and 100% greater efficacy in reducing cellular ROS in a human skin cell line (see Figure 3) when compared to synthetic melatonin, most likely due to the other constituents found in phytomelatonin such as chlorophyll, beta-carotene, lutein, and other protective, antioxidant phytonutrients [values derived from the original data presented in (1).]

Figure 1. Inhibition of inflammation by phytomelatonin (blue bar) and synthetic melatonin (gray bar).  Data are expressed as a percentage of human recombinant COX-2 inhibition.  Amounts used for each were 0.030mL (5mg/mL). 

Figure 2. Free Radical Scavenging Percentage (DPPH%) by phytomelatonin (blue bar) and three synthetic melatonins (gray bars). Data are expressed as mcg/mL. 

Figure 3. ROS fluorescence in human skin cell line by phytomelatonin (blue bars) and synthetic melatonin (gray bars). Data are expressed as ROS fluorescence using 50 mcg/mL. 

Figure 4. Oxygen radical absorbance capacity (ORAC) of two samples of phytomelatonin (blue bars) and three types of synthetic melatonin (gray bars). 

  *The phytomelatonin used for comparison is the proprietary format utilized in (1).

Authors: Deanna Minich, Ph.D., Melanie Henning, ND, Catherine Darley, ND, Mona Fahoum, ND, Corey B. Schuler, DC, James Frame

Reviewer: Peer-review in Nutrients Journal

Last updated: September 22, 2022




1. Kukula-Koch W, Szwajgier D, Gaweł-Bęben K, Strzępek-Gomółka M, Głowniak K, Meissner HO. Is phytomelatonin complex better than synthetic melatonin? The assessment of the antiradical and anti-inflammatory properties. Molecules. 2021;

2. Pérez-Llamas F, Hernández-Ruiz J, Cuesta A, Zamora S, Arnao MB. Development of a phytomelatonin-rich extract from cultured plants with excellent biochemical and functional properties as an alternative to synthetic melatonin. Antioxidants. 2020;9(2).

3. Wilson LM, Tharmarajah S, Jia Y, Semba RD, Schaumberg DA, Robinson KA. The Effect of Lutein/Zeaxanthin Intake on Human Macular Pigment Optical Density: A Systematic Review and Meta-Analysis. Vol. 12, Advances in Nutrition. 2021.

4. Mrowicka M, Mrowicki J, Kucharska E, Majsterek I. Lutein and Zeaxanthin and Their Roles in Age-Related Macular Degeneration—Neurodegenerative Disease. Vol. 14, Nutrients. 2022.

5. Meissner H. O. Personal Communication. Analytical Resource Laboratory. West Valley, UT; 2021.

6. Sofic E, Rimpapa Z, Kundurovic Z, Sapcanin A, Tahirovic I, Rustembegovic A, et al. Antioxidant capacity of the neurohormone melatonin. J Neural Transm. 2005;112(3).

7. Rodriguez-Naranjo MI, Moyá ML, Cantos-Villar E, Garcia-Parrilla MC. Comparative evaluation of the antioxidant activity of melatonin and related indoles. Journal of Food Composition and Analysis. 2012;28(1).

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