Getting serious about sleep ingredients: Science experts share their picks for the most scientifically credible sleep ingredients

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Along with high-fives, karaoke night, and the joy of sharing an ice cream cone, one of the simple pleasures that COVID-19 has stolen from us in the past year is the benefit of a good night’s sleep.

And that benefit is substantial, as a good night’s sleep is more than just a simple pleasure; sleep scientists deem it a fundamental determinant of long-term wellness. Yet ironically, it’s precisely now, when restorative sleep feels so scarce, that we need its benefits the most.

Fortunately, we don’t have to wait for the pandemic to pass to start snoozing more soundly—and some of the credit for that goes to the dietary supplement industry.

As David J. Foreman, RPh, president, Herbal Pharmacist Media (Oceanside, CA), says, “Dietary supplements can play a large role in sleep issues. While they don’t erase the mental-health side of sleep problems, they can help mitigate some of the challenges.”

Forty Winks and More

So convinced of sleep’s significance is Michael A. Grandner, PhD, MTR, that he practically waxes poetic when describing it.

“Sleep is a fundamental part of our biology,” says the director of the Sleep & Health Research Program and Behavioral Sleep Medicine Clinic and associate professor of psychiatry at the University of Arizona College of Medicine (Tucson, AZ). “It’s like breathing air, eating food, and drinking water. It touches so many different systems within our bodies, from mental health and longevity to inflammation and brain function.”

So when our sleep hygiene takes a hit, our bodies and minds feel it.

The Centers for Disease Control and Prevention (CDC)¹ says that adults who qualify as “short sleepers”—sleeping less than seven hours per 24-hour period—are more likely to report being obese, physically inactive, and current smokers than are those who get sufficient sleep, or at least seven hours within each 24. Short sleepers are also more likely to report suffering from 10 chronic health conditions, including coronary heart disease, asthma, and depression, than are people who sleep sufficiently.

And while experts claim that adolescents need eight to 10 hours of sleep nightly, research shows that more than two-thirds of American high-school students report getting less than the lower bounds of that recommendation on school nights.^2,3

Can’t Stress It Enough

Perhaps most alarming, given the ongoing pandemic, is that poor sleep can tip levels of important hormones and neurotransmitters out of balance, and the stress that results from that imbalance can wreak havoc on the immune system.

For example, poor sleep elevates levels of the key stress hormone cortisol. Coupled with excess activity in the hypothalamic-pituitary-adrenal axis, the effects “can deplete the immune system,” says Miles Sarill, MSc, scientist at CV Sciences (San Diego).

Added stress also hinders our ability to produce melatonin, an antioxidant, hormone, and neurotransmitter that not only regulates sleep and circadian rhythms but modulates gut and immune health, too. “Emergent research demonstrates melatonin’s role as an important immunomodulator with potential antiviral effects,” Sarill points out, “so it’s important that we sleep well if we want to support a healthy immune system.”

But sleep may wield just as potent a regulatory influence over immune function even more directly upon our immune systems, with associations between short sleep duration, infection risk, and reduced immune-cell activity—namely, decreased levels of leukocytes, monocytes, lymphocytes, and lymphocyte subsets like B cells, T cells, and NK cells—showing up in the scientific literature.⁴

Research implicates as little as one night of total sleep deprivation in decreasing neutrophil function⁵, and suggests that prolonged sleep curtailment and the subsequent stress response can lead to immunodeficiency.⁶

Alas, Foreman concludes, “During these challenging times, stress, poor diets, lack of exercise, and even decreased spirituality are all contributing to sleep challenges.” Which is why strategies to overcome them are more in demand than ever.

Fortifying Sleep

Grandner notes that non-pharmaceutical strategies can suit many kinds of sleep problems—and are often what experts such as himself recommend.

“Behavioral strategies can be especially effective for insomnia,” he notes, “and there are many ways that dietary and supplement products may support sleep health. Although the scientific evidence doesn’t suggest a ‘miracle’ supplement that cures all sleep problems, a healthy diet can improve sleep quality.”

As a scientist at a company with an active drug-development division, CV Sciences’ Sarill is well aware of emerging research suggesting that botanical extracts targeting various neurotransmitter systems—the GABAergic, glutamatergic, serotonergic, and endocannabinoid systems among them—may prove useful. “Additionally,” he says, “certain botanicals and nutraceuticals work through other peripheral mechanisms to help with improved sleep hygiene.”

And Foreman invests most of his confidence in supplements that attack underlying stress rather than in ingredients that merely induce drowsiness. “When it comes to making recommendations, I’d rather address sleep from the root of the problem than just sedate someone with herbs like valerian or passionflower,” he says. “Who wants to be impaired?”

Rest Assured

It’s a good question, and it underscores the risk that sleep-supplement brands court when they formulate with ingredients that don’t deliver what users expect.

“Sometimes I overhear conversations from rightfully skeptical consumers about the safety or efficacy of sleep supplements that go something like, ‘None of these pills work!’” laments Sarill. It falls to responsible brands to correct that perception, and to promote ingredients with both a deep research basis and a novel story, he says.

Foreman agrees. “We don’t do the consumer any good by recommending an ingredient without scientific substantiation for proper dosing, duration, safety, and more,” he says. “We’re even opening the door to defeat and decreased trust in the dietary supplement industry.”

Grandner wants to see more “independently conducted, randomized, placebo-controlled trials with number of subjects and stringent control needed to produce reliable data on emerging sleep ingredients. Although these studies are rare, we need to encourage industry to invest in this type of research, and consumers need to demand it,” he says. “Small proof-of-concept studies are great, but they should just be a starting point.”

Finally, Sarill says, focus ingredients with what he calls polypharmacology. “Most pharmaceutical drugs are designed to hit one target,” he explains, “but many scientists understand that pathological states—including insomnia or anxiety—may stem from multiple aberrant biochemical pathways needing support. One of the strengths of natural products is their ability to gently affect multiple targets, transcription factors, enzymes, and receptors. And often, their targets are pathways that trigger our bodies’ own reparative processes.”

That’s an encouraging thought, and one that sleep experts applaud. As Grandner says, “With the nutrition industry focusing more on the potential for stress reduction and sleep promotion, I anticipate some interesting and creative approaches to helping the many out there who struggle with these problems.” That alone should put our minds at rest.

We asked science-centered experts to share their picks for the most exciting—and scientifically credible—sleep ingredients on their radars. Here’s what they told us.

CBD

“Phytocannabinoids derived from the hemp plant have gained tremendous popularity since passage of the 2018 Farm Bill, which removed many of the limitations to hemp cultivation,” CV Sciences’ Sarill says. CBD, or cannabidiol, is the most high-profile of these phytocannabinoids—not least for its calming-, relaxing-, and sleep-enhancing properties.

“CBD may promote relaxation through a number of different mechanisms,” Sarill notes, “and a recent placebo-controlled, randomized clinical trial⁷ demonstrated that supplementation with 15 mg of hemp-soured CBD”—provided by CV Sciences—“improved sleep quantity and quality, general wellness, and metabolic parameters such as HDL cholesterol.”

While he notes that FDA hasn’t yet given CBD the go-ahead as a dietary ingredient, that hasn’t stopped brands from using hemp-sourced CBD in their sleep-friendly products.

Lactium

Topping Foreman’s list of exciting sleep ingredients is Lactium, a casein hydrolysate produced and marketed by Ingredia (Wapakoneta, OH).

The ingredient “has great science⁸ and is most specific to sleep,” Foreman notes, and according to the company, its secret to success is a bioactive decapeptide called alpha-casozepine that has soothing properties. Other benefits of the product, Ingredia claims: decreased anxiety symptoms and improved emotional regulation—all without drowsiness, sedation, memory loss, habituation, or addiction.

L-theanine

This non-proteinogenic amino acid found in green tea has a solid reputation for its calming properties. As Sarill explains, “Due to its similarity to the excitatory amino acid and neurotransmitter glutamate, it binds glutamate receptors without activating them, limiting the potential for over-excitation.”

Atop those calming effects, L-theanine may also promote learning. “In 2011, a randomized controlled trial⁹ demonstrated that theanine supplementation was useful in helping some aspects of sleep in children diagnosed with ADHD,” Sarill adds.

Ashwagandha

Foreman finds the science¹⁰ behind Natreon’s (New Brunswick, NJ) Sensoril ashwagandha’s benefits compelling, noting that the botanical not only helped study participants with stress, but improved their sleep quality and quantity. The fact that its low effective dose—125 mg—can be taken in the morning and increased if needed is also a boon.

Foreman emphasizes that adaptogenic botanicals like ashwagandha “are not sleep supplements per se, but help with it indirectly—and this is becoming even more of a place to start than just ‘knocking someone out.’” He looks forward to learning whether or not other adaptogens “will prove their benefits beyond stress and show help in the sleep area, too.”

Melatonin

Savvy supplement consumers recognize melatonin not only as the endogenous hormone and neurotransmitter associated with sleep, but “as a common ingredient in dietary supplements marketed for sleep,” Sarill says.

Longstanding research¹¹ shows that just 0.3 mg—10 times less than you’d find in most sleep supplements—“may be effective for maintaining a healthy circadian rhythm,” he notes. “But as melatonin is being assessed as an immunomodulator, current studies¹² are assessing its efficacy as an adjunctive therapy in respiratory immune challenges—such as COVID.”

Magnesium

A mineral that’s good for sleep? Quite possibly so. Foreman is intrigued by the science hinting at a role for magnesium in balancing neurotransmitters, improving sleep and ameliorating not just stress but restless legs, too.^13,14

References

1. Centers for Disease Control and Prevention website. “Sleep and Sleep Disorders.” Last updated May 2, 2017. Accessed here.
2. Paruthi S et al. “Recommended amount of sleep for pediatric populations: a consensus statement of the American Academy of Sleep Medicine.” Journal of Clinical Sleep Medicine, vol. 12, no. 6 (June 15, 2016): 785-786
3. Wheaton AG et al. “Sleep duration and injury-related risk behaviors among high school students — United States, 2007–2013.” Morbidity and Mortality Weekly Report, vol. 65, no. 13 (April 8, 2016): 337–341
4. Besedovsky L et al. “The sleep-immune crosstalk in health and disease.” Physiological Reviews, vol. 99, no. 3 (July 1, 2019): 1325–1380
5. Morey JN et al. “Current directions in stress and human immune function.” Current Opinion in Psychology, vol. 5 (October 1, 2015): 13‐17
6. Besedovsky L et al. “Sleep and immune function.” Pflügers Archiv, vol. 463, no. 1 (January 2012): 121‐137
7. Lopez HL et al. “Effects of hemp extract on markers of wellness, stress resilience, recovery and clinical biomarkers of safety in overweight, but otherwise healthy subjects.” Journal of Dietary Supplements. Published online May 27, 2020.
8. Kim HJ et al. “A double-blind, randomized, placebo-controlled crossover clinical study of the effects of alpha-s1 casein hydrolysate on sleep disturbance.” Nutrients, vol. 11, no. 7 (June 27, 2019): 1466
9. Lyon MR et al. “The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial.” Alternative Medicine Review, vol. 16, no. 4 (December 2011): 348-354
10. Auddy B et al. “A standardized Withania somnifera extract significantly reduces stress-related parameters in chronically stressed humans: a double-blind, randomized, placebo-controlled study.” JANA, vol. 11, no. 1 (2008): 50-56
11. Zhdanova IV et al. “Effects of low oral doses of melatonin, given 2-4 hours before habitual bedtime, on sleep in normal young humans.” Sleep, vol. 19, no. 5 (June 1996): 423-431
12. Rodriguez-Rubio M et al. “A phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in patients with COVID-19 admitted to the intensive care unit (MelCOVID study): a structured summary of a study protocol for a randomized controlled trial.” Trials, vol. 21, no. 1 (August 5, 2020): 699
13. Abbasi B et al. “The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial.” Journal of Research in Medical Sciences, vol. 17, no. 12 (December 2012): 1161-169
14. Cao Y et al. “Magnesium intake and sleep disorder symptoms: findings from the Jiangsu Nutrition study of Chinese adults at five-year follow-up.” Nutrients, vol. 10, no. 10 (September 21, 2018): 1354