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    Thursday, April 2
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    Home»Supplements»Results of Human Clinical Research
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    Results of Human Clinical Research

    8okaybaby@gmail.comBy 8okaybaby@gmail.comApril 2, 2026No Comments5 Mins Read
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    Results of Human Clinical Research
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    In June of 2024 I wrote an article for Vitamin Retailer called, “Synthetic Melatonin vs. Phytomelatonin: The Scientific Difference,” in which I made a case for the advantages of plant-sourced phytomelatonin over conventional, synthetic melatonin. Since then, there have been studies on phytomelatonin from two different sources, expanding upon my earlier argument. That is what this current article is all about.

    Summary of My Previous Article

    In the aforementioned article, I reviewed the multitudinous studies on melatonin supplementation for sleep. I also defined phytomelatonin as being melatonin from plant source (plants make melatonin as part of their light/dark cycles). In addition, I explained that, in addition to phytomelatonin, a plant extract also has other naturally occurring, beneficial compounds. For example, a St. John’s wort source of phytomelatonin (Somnatural, Nutraland USA) also contains 2-hydroxymelatonin (good for bone health) and N-acetylserotonin (neuroprotective), while a tomato fruit extract source of phytomelatonin (Somato, Nutraland USA) also contains lycopene and GABA. Conversely, synthetically produced melatonin may also contain small amounts of other compounds that aren’t desirable (see my previous article for more details). So now let’s look at the new phytomelatonin studies

    Study on Phytomelatonin From St. John’s Wort Extract

    A six-week, randomized, double-blind, placebo-controlled, decentralized clinical trial1 was conducted using an online platform w/validated questionnaires involving 1,233 adult participants with sleep problems. There were four intervention groups: 1 mg phytomelatonin from Somnatural (extracted from St. John’s wort, Nutraland USA), 3 mg phytomelatonin from Somnatural, 10 mg synthetic melatonin and placebo. Objectives included, but were not limited to, sleep problems such as falling asleep and sleep restlessness. Results differed depending upon the cohort, but some preliminary findings were as follows. In a cohort of participants who already used pharmaceuticals, over the counters, supplements or cannabinoids to treat sleep disturbances, and who had sleep problems over the past seven days, 1 mg Somnatural phytomelatonin and 10 mg synthetic melatonin outperformed placebo (both P<0.05). In a cohort of participants (n=358) who were diagnosed with a sleep disorder and worried about not being able to fall asleep in the past seven days, 1 mg and 3 mg Somnatural phytomelatonin significantly improved outcomes relative to baseline (P<0.05); 10 mg synthetic melatonin did not. In pairwise comparisons, among participants (n=1,131) who reported sleep disturbances for three months or longer and reported restless sleep in the past seven days, 3 mg Somnatural phytomelatonin provided significant improvements and outperformed 10 mg synthetic melatonin (P=0.014). In conclusion, 1 mg and 3 mg of phytomelatonin from Somnatural generally performed as well as or outperformed 10 mg synthetic melatonin and placebo for certain sleep problems in specific cohorts.

    Study on Phytomelatonin From Tomato Fruit Extract

    This 28-day study2 was conducted as an interventional, open label, pilot trial to examine the effects of plant-based melatonin (phytomelatonin) from Somato tomato extract (Nutraland USA) on key physiological and psychological domains associated with sleep quality, autonomic function, and health-related quality of life (HRQoL). The sample of the study included 22 healthy men and women (mean age: 42 years) receiving 2 mg of phytomelatonin daily from Somato (a tomato extract). Using a decentralized, real-world evidence (RWE) design, the study integrated objective biometric data from Oura ring wearable devices with validated participant-reported outcomes (e.g., Pittsburgh Sleep Quality Index (PSQI) and HRQoL using Short Form 36 Health Survey (SF-36)) to explore tolerability, early efficacy signals, and mechanistic trends in a healthy adult population. Compared to baseline, results showed that participants were able to fall asleep 33 percent faster (p=0.005), spent less awake (p=0.002), had better sleep efficiency (p=0.011), and had an improved global PSQI score (p=0.025) (Figure 1). Significant improvement was also demonstrated for emotional well-being (p=0.02). In conclusion, this pilot study found that 2 mg/day of phytomelatonin from Somato tomato extract improved physiological and psychological domains associated with sleep quality, autonomic function and health-related quality of life (HRQoL).

    In addition, given the positive results of this pilot study, a larger, randomized controlled trial is currently underway to confirm and expand upon the benefits of Somato phytomelatonin from tomato fruit extract.

    Other Journal Commentary

    Furthermore, in a scientific journal article3 researchers proposed that phytomelatonin is a desirable alternative to synthetic melatonin: “The interest of this proposal arose from the need to avoid the unwanted by-products present in synthetic melatonin preparations. The substitution of synthetic melatonin by phytomelatonin in medical treatments could also lead to substantial improvements in the results.”

    Conclusion

    There is no question that consumers prefer nutraceuticals from natural sources over those from synthetic sources. Now, with human clinical studies to support them, natural plant sources of phytomelatonin from St. John’s wort and tomato fruit extract have been demonstrated to be effective for supporting different aspects of healthy sleep.VR

    References:

    1 Pauli EK, et al. A Randomized, Blinded, Placebo-Controlled Direct to-Consumer Study of Health and Wellness Products on Sleep and Other Health Outcomes. Radicle Science. 2024; unpublished.

    2 De Jesus M, Bergquist K, Bruno G. Effects of Somato TOMATO Fruit Extract on Key Physiological and Psychological Domains Associated with Sleep Quality, Autonomic Function, and Health-Related Quality of Life: A Pilot Study. Altern Ther Health Med. 2026 Jan;32(1):20-24. PMID: 40985949.

    3 Arnao MB, Hernández-Ruiz J. Phytomelatonin versus synthetic melatonin in cancer treatments. Biomed Res Clin Prac. 2018; 3(3):1-6.

    Gene Bruno, DBM, MS, RH(AHG) Professor Emeritus of Nutraceutical Science, is a writer, educator and a nutraceutical scientist with more than 45 years of experience educating natural product retailers and health care professionals and formulating natural products for dozens of dietary supplement companies. He has written articles on nutrition, herbal medicine, nutraceuticals and integrative health issues for trade, consumer magazines and peer-reviewed publications. Bruno also hosts “The Vitamin Professor Podcast” brought to you by VRM Media. He can be reached at [email protected].

    Clinical Human Research Results
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