Stress and sleep are two of the most important determinants of overall health. Many people have too much of the former, and not nearly enough of the latter.
Add in poor diet and lack of exercise, and you’ve got an equation for chronic disease.
People recognize that constant stress and poor sleep are inter-related, and that they are risk factors for metabolic dysregulation, obesity, CVD, and cognitive impairment. Prescription drugs to induce sleep and mitigate stress are themselves problem-fraught, and many people are self-treating with herbs and other supplements as alternatives.
There’s an astonishing array of non-Rx products promoted for stress management and sleep support. Some work, some don’t, and it is vital for clinicians to know which ingredients have strong evidence of efficacy and safety, says David Foreman, RPh.
A truly healthy night’s sleep consists of four to six total cycles through all 4 sleep stages, with 75% of total sleep time spent in non-REM states. That means a minimum of 7 hours of total sleep.
“In today’s fast-paced world, where stress and anxiety often hinder a good night’s sleep, many people seek natural remedies to improve their sleep quality,” says Foreman, known for his popular Herbal Pharmacist blogs and broadcasts. But they’re often treating themselves without understanding much about the phases of sleep and what happens during each stage.
Speaking at a recent Health & Longevity conference produced by Nutraceuticals World and Health and Personal Products Industry magazines, Foreman stressed that helping people sleep better is one of the most impactful things practitioners can do. Supplements can be valuable allies in this effort, provided you select them carefully and use them prudently.
The four key sleep stages are:
- N-1 Light Sleep (1-5 minutes): This is an initiatory phase of non-REM during which the body is slowly relaxing. Physical movement and brain activity decrease. Someone in N-1 sleep is easily roused, but if undisturbed, will easily pass into the N-2 phase.
- N-2 Light Sleep (10-60 minutes): This non-REM stage is characterized by a slowing of heart rate, a drop in body temperature, slower breathing, and a cessation of eye movements. Brain waves show a mix of sleep spindle patterns and K-complexes which help protect sleep from outside disturbances. It is more difficult to rouse someone in N-2.
- N-3 Deep Sleep (20-40 minutes): The third non-REM phase, often called deep or slow-wave sleep, is characterized by very slow breathing, full muscle relaxation, and low blood pressure. Brain activity shows delta wave patterns. This is the all-important restorative phase, during which the body directs energy and nutrients toward tissue repair and growth. It is critical for healthy immune system function, memory consolidation, and a host of other basic physiological and cognitive processes.
- Rapid Eye Movement (REM) (10-60 Minutes): During this phase, brain activity increases and shows patterns that closely resemble wakefulness. It manifests in the rapid eye movements which give this stage its name. Dreaming, which can occur in any stage of sleep, intensifies during REM. Notably, REM is accompanied by muscle atonia, which renders the body immobile and therefore less able to respond physically to what we are dreaming. Experts generally consider REM to be non-restorative, though it is important for memory and mood regulation.
The cycles repeat, in sequence, over the course of a night. The first cycle is often the shortest, ranging from 70 to 100 minutes total, while later cycles tend to fall between 90 and 120 minutes. And the duration of each sleep stage also changes over the night. During first cycles, the N3 stage lasts for 20 to 40 minutes. In later cycles, the N3 phases shorten and the REM phases lengthen.
According to the National Sleep Foundation, a truly healthy night’s sleep consists of four to six total cycles through all 4 sleep stages, with 75% of total sleep time spent in non-REM states.
“This means a minimum of seven hours of sleep. Ideally it should be more,” Foreman said. People who say they get “a solid five hours” and think they’re OK, are kidding themselves, he told conference attendees. Even one night of inadequate sleep can have measurable impact on immune system function. A chronic sleep deficit erodes overall health.
But for many people, a seven-hour night is the exception, not the rule. According to the Centers for Disease Control, roughly one-third of all American adults report that they routinely get less than 7 hours per night. Sleeplessness disproportionately affects non-Hispanic Black adults (43.5%) and young adults aged 25-44 (36.4%).
All forms of sleep disorders are on the rise in the US. According to the CDC, the prevalence of obstructive sleep apnea—one of the most problematic sleep-related conditions—rose by 41% from 2013 to 2016. To some extent this reflects greater public awareness and better detection. But other sleep problems like narcolepsy and hypersomnia are also rising.
Choosing from among the myriad supplements marketed as sleep aids can be a daunting challenge for practitioners and patients alike. There’s no simple one-size-fits-all product guaranteed to “work” for everyone, so the choices need to be individualized.
In his presentation, Foreman reviewed several of the most commonly used ingredients in sleep and stress-reduction supplements, and their general effects.
Melatonin: This is, arguably, the best-known sleep-related supplement ingredient, generating roughly $1.5 billion in global sales annually. An endogenous neurohormone that also has anti-oxidant and anti-inflammatory effects, melatonin regulates circadian rhythms, and many people take it to induce sleep, as a remedy for sleep-wake disorders, jet lag, or the negative consequences of shift work. Clinically, it has also been used to treat dementia, migraines, tinnitus, ADHD, autism, glaucoma, and even Covid (Minich D, et al. Nutrients. 2022).
Foreman said melatonin can be effective for helping some people get to sleep, however one should be aware that physiologically, melatonin levels are lowest in stages 3 & 4 and highest in the REM phase. Consequently, supplementing with melatonin can lengthen REM periods, meaning that the user may be sleeping longer but not spending as much time in the all-important restorative N-3 non-REM phases.
Gamma Aminobutyric Acid (GABA): Like melatonin, GABA is an endogenous inhibitory neurotransmitter that reduces neuronal excitability. It too has become a very popular sleep aid. Some products on the market combine GABA and melatonin, often with herbal ingredients as well. Supplemental GABA targets the GABAA receptors—the same receptors affected by benzodiazepines and barbiturates.
Many people using GABA find that it does help them to relax and fall asleep. Foreman recommended PharmaGABA®, a branded ingredient produced by Pharma Foods International, a Japanese raw materials supplier. It is available in products from a number of different brands including Designs for Health, Thorne, and Natural Factors.
Unlike melatonin, GABA can increase non-REM sleep by roughly 21%. But that effect is can be overshadowed by a 97% increase in REM, Foreman explained. Again, people taking GABA may find it relaxing but they may not be getting the restorative sleep they need. The impact of GABA supplementation is variable from person to person.
Supplementing with melatonin can lengthen REM periods, meaning that the user may be sleeping longer but not spending as much time in the all-important restorative N-3 non-REM phases.
L-theanine: Derived from green tea leaves, L-theanine is a naturally occurring amino acid that can boost endogenous production of GABA, dopamine, and serotonin, producing a calming and relaxing effect. A placebo-controlled study involving 30 healthy adults showed that 200 mg/d of L-theanine over four weeks yielded statistically significant reductions in sleep disturbances, use of prescription sleep drugs, and stress-related symptom scores, as well as improved verbal fluency and executive function. The ingredient used in this study was Suntheanine, produced by Taiyo International. Foreman noted that L-theanine tends to increase the amount of time people spend in the first and last phases of their sleep cycles.
Palmitoylethanolamide (PEA): PEA is a naturally occurring fatty acid amide that helps quell inflammation by down-regulating multiple proinflammatory and nociceptive pathways, and by inhibiting mast cell and glial cell activity. A 2020 clinical study of 74 people with chronic joint pain showed that compared with placebo, twice daily supplementation with 175 mg of PEA (Levagen+TM(morning and night), led to significant reductions in pain scores, and better mood scores. PEA lowered inflammatory markers and reduced mast cell activity.
Foreman noted that PEA can also increase duration of restorative non-REM sleep. This likely contributes to the improvements in muscle recovery and reduced muscle soreness observed in a study of healthy male athletes. PEA is a good option for people who have sleep problems due to chronic pain and inflammation.
Saffron (Crocus sativus): Studies on a standardized extract of saffron called affron®show that this unique ingredient can inhibit the reuptake of dopamine, norepinephrine, and serotonin. It can also increase endogenous melatonin production. A 28-day placebo controlled clinical study of 55 adults with self-reported poor sleep showed that at doses of 14 mg twice daily, affron improved sleep scores. The extract also improves mood and reduces anxiety.
Magnesium: Among its myriad benefits, magnesium modulates the hypothalamic-pituitary-adrenal (HPA) axis, reducing the release of cortisol while stimulating the production of melatonin. The result? Reduced anxiety, relaxation, and a general calming effect. A 2017 systematic review of 18 clinical trials studies concluded that magnesium supplementation can reduce anxiety, especially in individuals with magnesium deficiencies. One study found that magnesium reduced subjective stress levels in individuals with low baseline levels.
Magnesium can also be an effective sleep aid. A 2012 placebo controlled study of 46 elderly people with chronic insomnia showed that supplementation with 500 mg of elemental magnesium reduced insomnia severity scores, reduced sleep onset latency, increased sleep time, improved sleep efficiency, and reduced early morning awakenings. It also led to beneficial changes in objective measures like serum renin, melatonin, and cortisol.
A metanalysis published in 2017 concluded that while the overall evidence is not strong enough to support a firm recommendation of magnesium as an insomnia treatment, the available data lean toward the positive. The authors state that oral magnesium is inexpensive and widely available, and that RCT evidence does suggest that supplementation with less than 1 g quantities, up to three times a day, can improve some sleep parameters.
Magnesium modulates the hypothalamic-pituitary-adrenal (HPA) axis, reducing the release of cortisol while stimulating the production of melatonin. The result? Reduced anxiety, relaxation, and a general calming effect.
Ashwagandha (Withania somnifera): A mainstay herb in Ayurvedic medicine, Ashwagandha has shown promise for stress reduction and sleep improvement, especially in people with high chronic stress levels. Bioactive compounds in the root of this plant can modulate the hypothalamic-pituitary-adrenal (HPA) axis, reducing cortisol while activating GABAergic signaling pathways, thereby reducing anxiety and helping people relax. Ashwagandha also has antioxidant properties that promoting resilience against stress.
A 2019 double-blind, randomized controlled study of 60 adults showed that daily supplementation with 240 mg of a standardized Ashwagandha extract significantly reduced stress and anxiety, inducing 23-30% reductions in mean cortisol levels after 8 weeks. The anxiolytic effects can translate into better sleep, as shown in a 2020 clinical trial comparing 40 insomnia patients and 40 healthy controls. Both groups showed improvements in various sleep parameters, but the effects were more pronounced among those with insomnia.
There are a number of branded, standardized, Ashwagandha extracts widely used in dietary supplements. Two of the most well-researched are KSM-66 and Sensoril.
In his review, Foreman cited several other herbs and ingredients that people may be taking to manage stress and improve their sleep. These include: Valerian (Valeriana officinalis), which can increase restorative stage 3 non-REM; Caralluma fimbriata, a cactus-like plant that produces compounds that affect the hypothalamus, increasing serotonin while reducing cortisol; Holy Basil (Ocimum tenuiflorum), an herb known as Tulsi in Ayurvedic medicine that reduces cortisol and increases a sense of calm; and Kanna (Sceletium tortuosum), a succulent plant native to southern Africa, extracts of which are notable for their rapid-onset effects on the amygdala.
Foreman added that intensive research on the gut-brain axis is showing that certain probiotic strains are showing promise for stress-mitigating and sleep-improvement. Specifically, a placebo-controlled study of 120 healthy adults showed that five weeks of daily supplementation with Lacticaseibacillus paracasei (HOWARU Lpc-37™) resulted in significant reductions in perceived stress and an increased sense of calm.
Similarly, a strain of Lactiplantibacillus plantarum known commercially as HEAL9, improved sleep and indicators of cognitive function in a study of moderately stressed individuals.
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