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New Research Showing Plant Melatonin is up to 646% More Effective than Synthetic Melatonin

New Research Showing Plant Melatonin is up to 646% More Effective than Synthetic Melatonin

By Kim Ross, DCN, CNS, IFMCP

Reviewed by Deanna Minich, MS, PhD, FACN, CNS, IFMCP

December 29, 2022

Melatonin can be derived from three different sources, and the source can dramatically impact their effectiveness—even safety. As more people, and medical professionals, discover the broad benefits of melatonin, it’s smart to know the source of your supplement.      

“Melatonin” is a supplement derived from animal, synthetic, or plant sources. This is an important distinction as animal sources include melatonin derived from the pineal gland of cows, sheep, or pigs. Due to safety concerns of animal sources, synthetic melatonin has become more widely used and is currently the most common form of melatonin available on the market accounting for 99% of all melatonin on the market. However synthetic sources of melatonin involve industrial processing and may contain toxic substrates, contaminants, fillers, excipients, or even residual serotonin. But what is most important is that recent research comparing synthetic and plant melatonin has shown that melatonin from plants may be up to 646% more effective [1].      

Nature knows best

Research has proven that organic fruit and vegetables are free of residual pesticides and other chemicals that can cause cancer, endocrine disruption, and various other health issues. But the real news here is that they also contain higher levels of some vitamins, minerals and key compounds that positively impact our health.

This means that simply by choosing an organically-grown orange, we can simultaneously avoid consuming all the downsides of industrial farming, while potentially providing our bodies with higher levels of vitamin C, antioxidants, and other micronutrients.

As health-conscious consumers ourselves, nature knows best soon became our ethos. It began as a philosophy, but it quickly became a rational, deliberate choice that extended from the food we ate, to the water we drank, and the supplements we took…always looking for the highest quality, most bioavailable, most natural, organic, product we could find.

And melatonin was no different.

It may surprise you to learn that it wasn’t until 1995 [2] that melatonin was even discovered in plants, and it was only in 2008 that the first plant melatonin supplement (called Herbatonin®) was introduced, made from unique varieties of chlorella, alfalfa, and rice. However, this novel melatonin source, which accounts for less than 1% of melatonin sales, may in fact be the best-kept secret in supporting many areas of your health.

comparison chart of plant melatonin vs. synthetic melatonin, source, processing, contents, environmental safety, anti-inflammatory activity, anti-radical scavenging activity, ORAC score

Melatonin supports healthy sleep—and your health.

As a hormone, melatonin has long been recognized for the vital role it plays in supporting our body’s circadian rhythms and our sleep/wake cycle, which is intrinsically connected to nearly all aspects of our health. However, this is only a part of what melatonin does in our body. It also supports healthy inflammation and works as a powerful antioxidant, protecting our cells, DNA, and mitochondria, as well as supporting our immune system and fighting the aging process.*

Antioxidants: What they are and why they’re so important.     

Antioxidants can be found in fruits, vegetables, nuts, fish, and meat, and they play a key role in our health by actively scavenging and fighting unstable, damaging compounds in the body known as “free radicals.” Free radicals are produced in our bodies every day. They are the natural by-product or “waste” that results from metabolizing food into energy, cell repair after exercise or muscle strain, the absorption of oxygen from the air we breathe, and even the process required to eliminate toxins and chemicals from our bodies.

The “clean up” that antioxidants help our bodies perform is critical because waste takes its toll. When too many free radicals build up it can result in imbalanced inflammatory responses, cell and DNA oxidation, and increased aging.  This is why it is so essential to get enough antioxidants each day through the combination of a healthy diet and well-balanced supplements.*

Melatonin works more wonders than most other antioxidants.

Most antioxidants, like vitamin C, only work in one or two specific ways.

Melatonin works in all of the key ways our body needs antioxidants to work, from prevention of oxidant formation and interruption of the oxidative stress chain reaction. It also scavenges reactive oxygen species (ROS) stopping or delaying oxidation and it repairs oxidized and damaged molecules at the cellular level.*  

Even more important, unlike nearly all other antioxidants or any molecule for that matter, melatonin has a unique ability to cross the blood-brain barrier.* The blood-brain barrier is a naturally protective border that stops toxins, and many other molecules in our blood from crossing into our brain and nervous system. The challenge is that this border is so protective that it also blocks beneficial molecules.

But melatonin is unique. It's able to cross the blood-brain barrier because it’s soluble in both water and lipids (fat), which enables it to freely pass the barrier and flow through all of the body’s tissues and vital organs.

This significant finding is creating much excitement among scientists and the medical community, as very few molecules are able to do this.

free radical scavenging percentage (DPPH%) of herbatonin vs three other melatonin brands

What is even more exciting is that phytomelatonin (Herbatonin®) appears to have an even greater impact as an antioxidant than synthetic melatonin. Recent research [3] out of the Medical University of Lublin, in Europe, compared several sources of synthetic melatonin with Herbatonin®. It showed that Herbatonin was up to 470% more effective when looking at free radical scavenging potential (DPPH) and up to 958% more effective when comparing antioxidant oxygen radical absorbance capacity (ORAC).

Herbatonin® appears to possess significantly stronger antioxidant potential and free radical scavenging capacity as compared to synthetic melatonin according to emerging evidence.*

DPPH are organic compounds comprised of stable free radical molecules used to analyze antioxidant capacity [4,5].

The oxygen radical absorbance capacity (ORAC) score is a validated method used to measure the antioxidant capacity of foods and supplements (5). It is theorized that foods and supplements with a higher ORAC rating may be more effective at neutralizing free radicals. When too many free radicals build up, it can result in imbalanced inflammatory responses, cell and DNA oxidation, and increased aging.

Phytomelatonin (Herbatonin®) was compared to three synthetic melatonin sources for the ORAC score.

 oxygen radical absorbance capacity (ORAC) comparison between herbatonin and three other melatonin brands

As a comparison, the USDA reports the following ORAC scores for select foods [6]:

USDA report on ORAC scores for phytomelatonin, prunes, synthetic melatonin, blueberries, kale, red bell pepper, cherries

Cyclooxygenase-2 (COX-2) is the key enzyme induced in response to the inflammatory process, often resulting in discomfort [7]. The inhibition of COX-2 activity translates into reduced inflammation reactions and increased comfort.

In the study comparing synthetic and plant melatonin, Herbatonin® was 646% stronger at inhibiting COX-2 enzyme activity over synthetic melatonin [3]. It is plausible that the significantly stronger inhibition of COX-2 with Herbatonin® is due to the presence of other phytoactive compounds that naturally occur in plant melatonin, such as chlorophyll, beta-carotene, isoflavones, phytates, and saponins [3].

targeted inflammation inhibition (COX-2) of herbatonin compared to synthetic melatonin

Fight the effects of cell oxidation and aging

When researching anti-aging, cellular and mitochondria health you often hear about reactive oxygen species (ROS) which are natural by-products of our normal cellular function and metabolism. High levels of ROS result in oxidative stress and can cause oxidation to cells and DNA [8] which is why you always look for supplements to reduce ROS activity.

In the study we saw that Herbatonin® had up to 100% greater efficacy in reducing ROS compared to synthetic melatonin [3].

ROS fluorescence (cellular damage) in human skin cell line, herbatonin vs. synthetic melatonin

Your choice is easy when you know the benefits of plant melatonin

The quality and purity of the source of the things we use to nourish and support our body and health has a profound impact. Not just in relation to reducing the amount of toxins we add, but also in the efficacy and results we get from those foods or supplements. Choose plant Herbatonin® and you know you’ll be getting all the benefits of melatonin.


  1. 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:
  2. Arnao MB, Hernández-Ruiz J. The physiological function of melatonin in plants. Plant Signal Behav. 2006 May;1(3):89-95. doi: 10.4161/psb.1.3.2640. PMID: 19521488; PMCID: PMC2635004.
  3. 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 Oct 8;26(19):6087. doi: 10.3390/molecules26196087. PMID: 34641628; PMCID: PMC8512846.
  4. Kedare SB, Singh RP. Genesis and development of DPPH method of antioxidant assay. J Food Sci Technol. 2011 Aug;48(4):412-22. doi: 10.1007/s13197-011-0251-1. Epub 2011 Feb 25. PMID: 23572765; PMCID: PMC3551182.
  5. Huang D, Ou B, Prior RL. The chemistry behind antioxidant capacity assays. J Agric Food Chem. 2005 Mar 23;53(6):1841-56. doi: 10.1021/jf030723c. PMID: 15769103.
  6. McBride J. High-ORAC Foods May Slow Aging. [Internet]. USDA Agricultural Research Service. 2022 [cited 2022 Oct 4]. Available from:
  7. Simon LS. Role and regulation of cyclooxygenase-2 during inflammation. Am J Med. 1999 May 31;106(5B):37S-42S. doi: 10.1016/s0002-9343(99)00115-1. PMID: 10390126.
  8. Bardaweel SK, Gul M, Alzweiri M, Ishaqat A, ALSalamat HA, Bashatwah RM. Reactive Oxygen Species: the Dual Role in Physiological and Pathological Conditions of the Human Body. Eurasian J Med. 2018 Oct;50(3):193-201. doi: 10.5152/eurasianjmed.2018.17397. PMID: 30515042; PMCID: PMC6263229.

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