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Don’t believe us. Believe the research.

By Deanna Minich, PhD
Reviewed by Kim Ross, DCN

July 18, 2023

There are many schools of thought on approaches to melatonin. At Symphony Natural Health, we would like to propose not to believe our opinion but to know the decades-long lineage of melatonin research.

Our Medical Team has followed the research of melatonin experts like Russell Reiter, Ph.D., Professor of Cell Systems and Anatomy at the University of Texas Health Science Center; Richard Wurtman, MD, a Harvard-trained neuroscientist who spent his career at the Massachusetts Institute of Technology; and Paolo Lissoni, MD, a researcher, oncologist, endocrinologist, and internal medicine doctor. We also routinely review the latest literature on melatonin to provide the most up-to-date information to our practitioners.

There are several myths that have been continually circulating about melatonin. We want to set the record straight based on what is available in the science:

Myth #1: Melatonin is a hormone and, therefore, unsafe to take as a supplement.

This statement is a common misconception circulating on social media. Melatonin has been established as more than a pineal-derived hormone. Extensive research shows it is a mitochondrial regulator, antioxidant, and anti-inflammatory agent (1–6).

Melatonin occurs naturally in minute amounts in foods, especially nuts, seeds, fruits, and vegetables. It can be made in many parts of the body, especially the gut, which produces 400 times more melatonin than the pineal gland (6).

Clinically we can liken melatonin to Vitamin D, which is also considered a hormone, yet people take it as a dietary supplement daily. As we discussed in our Nutrients journal review article, the many similarities between vitamin D and melatonin. We refer to them as “circadian nutrients,” with vitamin D associated with sunlight and melatonin with darkness.

Like all hormones, if there is a concern, it is not over the hormone itself but ensuring patients and consumers are using a safe and effective dose. More on educating patients in Myth #4. Melatonin, therefore, is not to be “feared” as a hormone. It demonstrates potent anti-inflammatory, antioxidant, and free radical scavenging activities that make it versatile, particularly plant melatonin.

For more on supplementation with melatonin have a look at this melatonin research website.

Myth #2: If you take melatonin, it will stop your body from making it.

Research studies have shown that melatonin from supplementation does not impact endogenous production (7–10). Unlike other hormones, melatonin does not have a negative feedback loop. Instead, it is regulated by light/darkness.

Like vitamin D, where even taking therapeutic “super” doses will not impact the body’s production, therapeutic “super” doses of melatonin do not impact production. Dr. Lissoni, has seen this in his cancer research with short-term doses of 50 mg of melatonin per day (10). Similarly, this is also the case with other antioxidants like coenzyme Q10, where the body doesn’t stop endogenous production when you start taking exogenous supplements (11).

It’s well known that nutrients, including vitamin D and CoQ10, as well as melatonin, decline with age, often coinciding with increased rates of chronic diseases, which speaks to the need to replenish lost reserves (6,11,12).

There is evidence that taking melatonin long-term in high doses can reduce the sensitivity of melatonin receptor sites (13), which is why we advocate for physiological doses of 0.3 mg when using melatonin long-term. Of note, much of the literature on high-dose melatonin is for short-term use for aggressive concerns such as cancer, viruses, and sepsis or to evaluate the safety of melatonin (14–18).

For more research that shows endogenous production is not impacted by exogenous melatonin supplementation, read this.

Myth #3: All melatonin is “created equal.”
It is not.

Melatonin has many sources (synthetic, animal, plant, microbial) and many forms (sublingual, standard, delayed release, sustained release, transdermal, etc.) with varying stability and quality. More information on the diversity of formats is at this link.

Most melatonin is synthetic. As part of the processing, it can contain contaminants like serotonin. Animal-derived melatonin has other concerns related to prions. Plant-based sources can start with a plant source like corn and then be chemically synthesized or spiked with synthetic melatonin and/or contain pesticides. Getting certificates of analysis from your supplier for the exact product you are using is a fair request as you build trust with the manufacturer of the melatonin supplement you choose.

The melatonin in HerbatoninPRO™ is from the plant’s cell matrix, is bioidentical to human melatonin, and is free of all allergens and toxins while being GMP-certified, vegan, kosher-certified, and non-GMO. As a plant melatonin, it contains nutrients naturally occurring in the plant (Image 1).

Image 1: Macro, micro, and phytonutrients in plant melatonin

Image credit: Minich DM, Henning M, Darley C, Fahoum M, Schuler CB, Frame J. Is Melatonin the "Next Vitamin D"?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. Nutrients. 2022;14(19):3934. Published 2022 Sep 22. doi:10.3390/nu14193934. https://creativecommons.org/licenses/by/4.0/

Our Certificate of Analysis for Herbatonin

We also encourage you to look for third-party accreditation such as NSF, GMP, or consumer groups like ConsumerLab to verify product and process, not just for melatonin but all supplements.

For a comprehensive comparison of Herbatonin and synthetic melatonin, on PubMed, view Dr. Deanna Minich’s webinar or access PubMed research on the topic Molecules. 2021 Oct; 26(19): 6087.

Myth #4: People/clinicians aren’t savvy enough to understand the nuance of dosing

There is a new trend, primarily from manufacturers of sleep supplements without melatonin, and podcasters with sensationalistic SEO strategies, to spread misinformation and instill fear about melatonin and “side effects.” When pressed, many of these people or companies capitulate and acknowledge that melatonin is indeed beneficial for many areas of health, however, in low physiological doses, for specific demographics of people, and for particular health conditions.

Instead of empowering people with nuance and a deeper understanding of their body and health, influencers and, some educators are just providing a blanket statement of “melatonin is bad,” just like “hormones are bad” was the catch cry for the following decade after the WHI study on HRT in 2002. Let’s not make that same mistake again, and trust that we can educate and empower people about their health to make informed decisions.

The dosing of melatonin should be treated just as the dosing of all other supplements, medications, nutrients, food, caffeine, and alcohol should be. What is the appropriate dose for the person in need, and what does the literature tell us? As we know, many questions have arisen from practitioners, Dr. Kim Ross provided a comprehensive review of the research regarding dosing in the Clinical Webinar series entitled Melatonin Therapy: Anti-Aging, Longevity, Immune Health. You will hear these details in the second half of the webinar when the Q&A begins.

Get the facts on melatonin in our Melatonin Clinical Webinar Series here. Topics include:

• Is Melatonin the Next Vitamin D? with Dr. Deanna Minich

• Melatonin and Children: Clinical Applications, Dosing, and Safety with Dr. Mona Fahoum

• Do Your Patients Have a Darkness Deficiency? Slee, Circadian Rhtym, and Chronic Disease with Dr. Catherine Darley

• Melatonin Therapy: Anti-Aging, Longevity Immune Health with Dr. Kim Ross

References

1. Martín Giménez VM, de las Heras N, Ferder L, Lahera V, Reiter RJ, Manucha W. Potential Effects of Melatonin and Micronutrients on Mitochondrial Dysfunction during a Cytokine Storm Typical of Oxidative/Inflammatory Diseases. Diseases. 2021;9(2).

2. 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;

3. Budkowska M, Cecerska-Heryć E, Marcinowska Z, Siennicka A, Dołęgowska B. The Influence of Circadian Rhythm on the Activity of Oxidative Stress Enzymes. Int J Mol Sci. 2022;23(22).

4. Tan DX, Reiter RJ, Zimmerman S, Hardeland R. Melatonin: Both a Messenger of Darkness and a Participant in the Cellular Actions of Non-Visible Solar Radiation of Near Infrared Light. Biology (Basel). 2023 Jan 6;12(1):89.

5. Tan DX, Manchester LC, Esteban-Zubero E, Zhou Z, Reiter RJ. Melatonin as a potent and inducible endogenous antioxidant: Synthesis and metabolism. Molecules. 2015.

6. Minich DM, Henning M, Darley C, Fahoum M, Schuler CB, Frame J. Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements. Nutrients [Internet]. 2022;14(19). Available from: https://www.mdpi.com/2072-6643/14/19/3934/htm

7. Zisapel N, Lemoine, Garfinkel D, Laudon M, Nir. Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal. Ther Clin Risk Manag. 2011 Jul;301.

8. Mallo C, Zaidan R, Faure A, Brun J, Chazot G, Claustrat B. Effects of a four-day nocturnal melatonin treatment on the 24 h plasma melatonin, cortisol and prolactin profiles in humans. Acta Endocrinol (Copenh). 1988 Dec;119(4):474–80.

9. Matsumoto M, Sack RL, Blood ML, Lewy AJ. The amplitude of endogenous melatonin production is not affected by melatonin treatment in humans. J Pineal Res. 1997 Jan;22(1):42–4.

10. Lissoni P, Rovelli F, Pittalis S, Casati M, Giani L, Barni S, et al. [Therapy with melatonin does not suppress its endogenous production in healthy volunteers]. Recenti Prog Med. 1999 Feb;90(2):84–5.

11. Barcelos IP de, Haas RH. CoQ10 and Aging. Biology (Basel). 2019 May 11;8(2):28.

12. Gallagher JC. Vitamin D and Aging. Endocrinol Metab Clin North Am. 2013 Jun;42(2):319–32.

13. Sweis D. THE USES OF MELATONIN. Archives of Disease in Childhood - Education and Practice. 2005 Oct 1;90(3):ep74–7.

14. Menczel Schrire Z, Phillips CL, Chapman JL, Duffy SL, Wong G, D’Rozario AL, et al. Safety of higher doses of melatonin in adults: A systematic review and meta-analysis. Vol. 72, Journal of Pineal Research. 2022.

15. Malhotra S, Sawhney G, Pandhi P. The therapeutic potential of melatonin: a review of the science. MedGenMed. 2004 Apr 13;6(2):46.

16. Tan DX, Hardeland R. Estimated doses of melatonin for treating deadly virus infections: focus on COVID-19. Melatonin Research. 2020 Jun 3;3(3):276–96.

17. Gurunathan S, Qasim M, Kang MH, Kim JH. Role and Therapeutic Potential of Melatonin in Various Type of Cancers. Onco Targets Ther. 2021 Mar;Volume 14:2019–52.

18. Li Y, Li S, Zhou Y, Meng X, Zhang JJ, Xu DP, et al. Melatonin for the prevention and treatment of cancer. Oncotarget. 2017 Jun 13;8(24):39896–921.