Pistachio nuts are a rich source of naturally-occurring melatonin, and Australian researchers have shown that supplementation with pistachio-derived melatonin is equally effective in improving sleep parameters, as more the widely available synthetic forms of melatonin.
Some cultivars of pistachio (Pistacia vera, Anacardiaceae) naturally produce as much as 223 µg/g of phytomelatonin. That fact prompted Network Nutrition, an Australian nutritional ingredient company, to develop ProsomnialTM, an extract which delivers 1 mg of pistachio-derived melatonin per 100 mg dose.
Amanda Rao, PhD, director of RDC Clinical, a Brisbane-based clinical research organization, in collaboration with David Briskey at the University of Queensland, Brisbane, compared the absorption kinetics and clinical impact of Prosomnial head-to-head against equal doses of a synthetic melatonin supplement in a cohort of 26 generally healthy adults (mean age 31 years).
All subjects had mild but chronic sleep impairment, mostly prolonged wakefulness greater than 20 minutes, when trying to fall asleep.
The participants were not using any other sleep or anxiety-related pharmaceuticals or dietary supplements at the time of the study. Neither did they have any other medical conditions or prescriptions that might interfere with sleep.
Direct Comparison
The study followed an active-control crossover design: the patients were randomized to take either Prosomnial (100 mg) or a synthetic melatonin (100 mg) in visually identical gummy form, for 7 days. Both delivered 1 mg of melationin per 100 mg dose.
After a 14-day washout period, they did a second 7-day trial, this time using the alternative supplement. In all cases, they were told to take the assigned supplements every night, one hour prior to bedtime.
The participants had a total of three in-person clinic visits, as well as interim phone check-ins with the research teams. They also completed 7-day self-assessed sleep diaries during each of the two treatment phases.
During the second in-person visit, which followed the first treatment period, the patients were told to arrive in a fasting state, so investigators could measure baseline and post-dose plasma melatonin levels. They took readings at 10, 20, 30, 45,
“These data suggest that, in healthy adults with mild sleep-onset difficulties, a 1 mg dose of plant-derived melatonin (Prosomnial) is absorbed similarly to synthetic melatonin, and short-term sleep-related outcomes are comparable to an equivalent 1 mg synthetic melatonin gummy.”
–Amanda Rao & David Briskey
and 60 minutes following ingestion of a test dose of the assigned supplements. After the second treatment period, they repeated this assessment process.
Equivalent Impact
Compared with the pistachio product, the synthetic form of melatonin showed a trend toward higher peak plasma concentrations, but this difference was not statistically significant.
The area under the curve (AUC) for absorption from 0 to 2 hours was 5,994 pg·h/mL for Prosomnial and 7,425 pg·h/mL for the comparator (P = 0.39). Time to maximum plasma concentration was similar between the products (75 and 60 minutes, respectively; P = 0.93).
In terms of what really matters—the subjects’ sleep health—there were no significant differences between Prosomnial and the synthetic product. Rao and Briskey report that Prosomnial was associated with significant improvements from baseline in sleep latency, total sleep time, sleep quality, and a sense of being rested upon waking.
The synthetic melatonin reduced the number of nighttime awakenings and increased the feeling of being rested in the morning, but there were no significant changes in sleep latency or total sleep time.
Neither product gave meaningful changes in daytime nap frequency or duration, compared to baseline.
The investigators report no adverse events associated with either intervention, and no product-related safety concerns.
“These data suggest that, in healthy adults with mild sleep-onset difficulties, a 1 mg dose of plant-derived melatonin (Prosomnial) is absorbed similarly to synthetic melatonin, and short-term sleep-related outcomes are comparable to an equivalent 1 mg synthetic melatonin gummy,” they write.
The study, which was funded by Network Nutrition, does have limitations which the authors clearly acknowledge: it was a short-term trial; the subjects were generally healthy and not plagued by severe insomnia; assessment of sleep outcomes was based on subjective self-reporting; and there was no placebo arm against which to compare effect sizes.
Meeting a Need
But it does present some important observations, given that sleep problems affect millions of people. A 2024 survey by the American Academy of Sleep Medicine puts the prevalence of chronic insomnia at 12% of the US adult population.
Many of these people are either fed up with prescription sleep drugs or afraid to even try them. They are actively looking for safe, natural alternatives. The US sleep supplement market is expected to reach $1.45 billion in sales by 2029. Melatonin accounts for a major segment of that market.
The problem is that there is tremendous variability in melatonin product sourcing, quality and dose consistency. And since by and large, people are self-diagnosing and self-treating with melatonin, the clinical community has voiced major concerns about over-use, especially in children.
If pistachios are so rich in melatonin, is it possible to obtain impactful levels simply by eating more of the nuts? The answer is: Yes and No.
There’s no question that melatonin plays key roles in regulating circadian rhythms. As Rao and Briskey note, “This versatile molecule acts as an indolamine hormone primarily synthesized by the pineal gland…influencing various body systems and physiological processes that, in turn, induce immediate physiological responses. Melatonin exerts this influence by activating highly sensitive receptors MT1 and MT2 in response to changes in the light-dark cycles, directly affecting the synchronisation of circadian rhythm, sleep-wake cycles, and the duration and stages of sleep experienced.”
Activation of MT1 receptors reduces activity in the suprachiasmatic nucleus (SCN), which promotes sleep initiation. MT2 receptor activation regulates the synchronization of circadian rhythm in response to environmental cues, such as levels of ambient light.
“The synergistic action of these receptors in regulating sleep timing, duration, and circadian rhythms underscores their potential as valuable pharmacological targets aimed at optimizing sleep management and quality.”
Generally speaking, melatonin absorption from oral supplementation—regardless of specific melatonin form—averages around 15%, and it can vary between individuals. Absorption may be affected by age, caffeine consumption, tobacco smoking, use of oral conctraceptives and some other prescription drugs, including fluvozamine.
Why Not Just Eat Nuts?
The positive findings for the pistachio-based Prosomnial supplement begs a significant question: If pistachios are so rich in melatonin, is it possible to obtain impactful levels simply by eating more of the nuts?
The answer is, Yes and No.
Research on the precise amount of melatonin in pistachios is limited. It may range from 0.0034 mg–23 mg of melatonin per 3.5-ounce serving. One 2014 study estimated that a 3.5-ounce (100-gram) serving of shelled pistachios provides about 23 mg, which is substantially higher than the levels found in some supplement products (typically 0.10 mg per dose), and could have meaningful impact on sleep.
But the amount of melatonin in pistachios varies by species, growing conditions, processing methods, and whether or not the nuts are raw or roasted.
For people with significant sleep impairment who need a circadian reset, eating pistachios alone will probably not do the trick. But for those with mild sleep impairment who are seeking a food-first approach, a one-ounce serving of pistachios (roughly 50 nuts) is a good place to start. Not only do these tasty nuts contain meaningful amounts of melatonin, they are also a good food source of magnesium and vitamin B6, both of which promote relaxation and better sleep.
Pistachios are not the only plant source of melatonin. Other common food sources include:
- Mushrooms: 4,300–6,400 ng/g
- Oats: 91 ng/g
- Basmati rice: 38 ng/g
- Cherries: 10–20 ng/g
- Tomatoes: 1–67 ng/g
- Walnuts: 0.1-4 ng/g
- Salmon: 4 ng/g
- Eggs: 2 ng/g
- Cow’s milk: 0.014 ng/g
Thank you to our friends at HerbalGram for spotting and publicizing the Prosomnial study.
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