The Latest on Sleep, Relaxation, and Mood Ingredients for Dietary Supplements

Psychobiotics
One interesting story in supplements for relaxation and improved mood is newer research suggesting that ingredients marketed for other uses may also be beneficial for reducing stress and boosting feelings of well-being. Four such ingredients are probiotics, turmeric, and the macular carotenoids lutein and zeaxanthin.

Probiotics, popular for their role in gut health and immune-system function, are increasingly studied for their potential for enhancing psychological health (and are, for this use, sometimes referred to as “psychobiotics”). Bérengère Feuz, marketing manager for probiotics supplier Lallemand Health Solutions (Montreal, QC, Canada), says her company has identified 16 human studies of probiotics’ effects on the brain-gut axis published between 2007 and 2016. Ten of these were conducted on healthy adults with “non-pathologic levels of stress,” Feuz explains, and the other six “concerned severe or pathological conditions and should be regarded at this stage mainly as proofs of concept of the role of probiotics and microflora in brain health.” 

One of the more recent studies, led by University of Florida’s Tyler Culpepper, PhD, and published in 2016, concluded that healthy university students receiving the probiotic strain Bifidobacterium bifidum Rosell-71 for six weeks during exam time had fewer bouts of stress-induced diarrhea as well as less sleeplessness. Additionally, during periods of very little sleep, participants taking the probiotic supplement reported lower stress levels than those taking the placebo.(1)

An earlier study published in 2010 by neuropsychopharmacologist Michael Messaoudi demonstrated the benefits of Lallemand’s Probio’Stick, containing Lactobacillus helveticus Rosell-52 and Bifidobacterium longum Rosell-175, on psychological symptoms of stress and anxiety.(2) Daily intake of the supplement for one month significantly improved general signs of anxiety and depression and the subjects’ ability to cope with the stress of everyday life, Feuz reports. Results were also correlated by a decrease of cortisol levels in the urine, a biomarker of stress.

Says Feuz, “Today, we believe that healthy adults represent the main target [for psychobiotic-supplement] applications.” She contends that the science thus far shows that probiotic supplements “could help moderate general feelings of anxiety and promote a healthy mood balance in those experiencing mild to moderate stress from life events.” 

References:
1. Culpepper T et al., “Bifidobacterium bifidum R0071 decreases stress-associated diarrhea-related symptoms and self-reported stress: a secondary analysis of a randomised trial,” Beneficial Microbes, vol. 7, no. 3 (February 2016): 327-336
2. Messaoudi M et al., “Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and Bifidobacterium longum R0175) in rats and human subjects,” British Journal of Nutrition, vol. 105, no. 5 (March 2011): 755-764

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Turmeric
Another well-known ingredient now attracting recognition for potential psychological benefits is turmeric (and more specifically, its active derivative curcumin). Curcumin is known for its anti-inflammatory properties as well as beneficial impacts on cardiovascular and joint health, but some recent research suggests its usefulness for neurological health. 

A study of 100 subjects published in Phytotherapy Research in 2014 by Yunes Panahi et al. concluded that a curcuminoids-piperine combination “is an effective addition to standard therapy for major depressive disorder and significantly improves the efficacy of treatment in alleviating depression symptoms.”(3) Some additional animal studies also point to curcumin’s potential neuroprotective activity. So far, it appears that curcumin’s reduction of oxidative stress may be the mechanism responsible for its mood-improvement benefits.



References:
3. Panahi Y et al., “Investigation of the efficacy of adjunctive therapy with bioavailability-boosted curcuminoids in major depressive disorder,” Phytotherapy Research. Published online August 4, 2014.

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Lutein and Zeaxanthin
The macular carotenoids lutein and zeaxanthin, whose positive effects on eye health were well established by the large-scale AREDS2 study completed in 2006, were recently the subject of a study investigating their effect on stress response and mood. Lynda Doyle, MS, senior vice president, global marketing, OmniActive Health Technologies (Morristown, NJ), marketer of the Lutemax 2020 ingredient combining lutein, RR-zeaxanthin, and RS meso-zeaxanthin, says a study published in February of this year in Nutritional Neuroscience was “the first of its kind to show that supplementation with Lutemax 2020 reduces physical markers of stress and improves emotional and physical indices of health in a healthy, young population.”(4)

The double-blind, placebo-controlled study was very small (59 subjects aged 18 to 25), but Doyle says the results indicated that supplementation with lutein and zeaxanthin for six months did “significantly decrease cortisol levels [and] improve psychological stress and emotional and physical health.”

As a result of this and other research, OmniActive now markets its macular carotenoids not just for eye-health formulations but for a broader range of supplements, including those for cognition, sleep, “protection against digital devices,” and stress.

References:
4. Stringham NT et al., “Supplementation with macular carotenoids reduces psychological stress, serum cortisol, and suboptimal symptoms of physical and emotional health in young adults,” Nutritional Neuroscience. Published online February 2017.

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Valerian
Ingredients for relaxation, improved mood, and better sleep are wide ranging, providing supplement makers with a wealth of options that include plant-derived, animal-derived, microbial, and mineral-based solutions. Botanicals appear to offer the greatest number of products for this category, and consumer demand for herbal and botanical supplements in general is holding strong, with the American Botanical Council’s HerbalGram journal reporting total U.S. retail sales of all herbal supplements at nearly $7 billion in 2015. From this same report, relaxation-related botanicals such as valerian root ranked among the top 40 best-selling herbal supplements in the U.S. mainstream multioutlet channel that year.

U.S. sales of valerian-root supplements reached about $6.2 million in the natural channel in 2015, a nearly 6% increase over the previous year, according to HerbalGram. Studies suggest that valerian is generally safe for use by most healthy adults for short periods of time, and “it has been shown to improve sleep in people with sleep problems,” states Michael Grandner, PhD, assistant professor of Psychiatry, Psychology, and Medicine, and director, Sleep & Health Research Program, University of Arizona College of Medicine. Indeed, a review of the existing scientific literature on valerian’s effectiveness for improved mood and sleep published in 2011 concluded that “there seems to be some evidence of the effectiveness of valerian for treating insomnia, which is limited by the quality of existing studies. Valerian root is well tolerated and safe, with infrequent and benign side effects.”(5) And an editorial published in the journal Menopause the same year maintains that valerian is also “safer than other sleeping pills. It does not impair morning reaction times, concentration, or coordination. Its most notable adverse effect is occasional mild headaches.”(6) (Valerian seems not to have attracted a lot of attention from the research community in the past five years or so, based on a review of the PubMed database.) 

While evidence doesn’t yet fully support valerian’s use as a treatment for insomnia, the plant has “a long history of use in adults,” says Erin Stokes, ND, medical director at MegaFood, which markets Dream Release sleep formula. Its contemporary uses include those for anxiety, sleeplessness, depression, and menopause.

References:
5. Taibi DM et al., “A systemic review of valerian as a sleep aid: safe but not effective,” Sleep Medicine Reviews, vol. 11, no. 3 (June 2007): 209-230
6. Regestein QR, “Is there anything special about valerian?” Menopause: The Journal of the North American Menopause Society, vol. 18, no. 9 (September 2011): 937-939

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Polyphenol Blend
A new proprietary “mind and body wellness” botanical formula created by Fytexia (Vendres, France) launched in September 2016 and combines extracts of yerba mate, green tea, grape, grapefruit, and black carrot with vitamin B3. The ingredient was recently examined in a four-month, double-blind, randomized clinical study consisting of 33 participants aged 30 to 50 years. Conducted in collaboration with University of Murcia in Spain, the study, while quite small, concluded that daily supplementation with the tea-and-botanicals blend, called HolisFiit, led to “significant increase in overall sleep quality through a facilitation of falling asleep and a significant increase in total sleep duration” for participants, in addition to “rebalancing” subjects’ ratio of lean-to-fat mass.(7)

Touting the polyphenol-rich blend’s versatility, Fytexia Sales and Marketing Director Sophie Loisel says that HolisFiit can be used in supplement capsules, tablets, instant powders, and ready-to-drink formulations; it will be targeted at supplements for individuals practicing yoga and other mind-body exercise, but also “to anyone in quest of a little help for a more balanced and active lifestyle,” she says.

References:
7. Romain C et al., “Regular consumption of HolisFiit, a polyphenol-rich extract-based food supplement, improves mind and body well-being of overweight and slightly obese volunteers: a randomized, double-blind, parallel trial,” International Journal of Food Sciences and Nutrition. Published online February 2017. 

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Spearmint
Another plant rich in polyphenols, spearmint, is also being marketed for psychological and sleep benefits. Research conducted by Kemin Human Nutrition and Health (Des Moines, IA) and the MusclePharm Sports Science Institute suggests that extracts from certain lines of this well-known plant aid both cognition and sleep. 

Neumentix Phenolic Complex K110-42, an extract produced from Kemin’s patented spearmint varieties, demonstrates “working-memory improvements” and sleep support in study subjects, says Kim Colletti, global cognition product manager, Kemin Human Nutrition and Health. “People who took Neumentix for benefits in working memory found they fell to sleep faster and easier at night. When [900 mg of Neumentix was] taken in the morning, participants reported that they got to sleep easier and faster at night compared with subjects who took placebo,” she explains, citing results of a 90-person study presented at the American Academy of Neurology Conference in 2015.(8)

Launched in 2014, Neumentix is a stable, water-soluble ingredient that is well suited to a variety of delivery formats, including such functional beverages as vegetable juice, coffee, and tea, as well as baked goods, beverage sticks, effervescents, chews, gummies, softgels, and capsules. Colletti attributes the formulation’s effectiveness to “four potential mechanisms of action: antioxidant defenses, protection of existing neurons, growth of new neurons, and nerve transmission.”

References:
8. Fonseca B et al., “Effects of a distinct phenolic complex on working memory performance in healthy men and women with age-associated memory impairment.” Poster Session VII: Aging, Dementia, Cognitive, and Behavioral Neurology: Clinical Trials. Presented at American Academy of Neurology Conference on April 23, 2015.

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L-theanine
An amino acid derived mainly from green and black tea, L-theanine offers “calming effects-without loss of alertness-that are felt almost immediately,” asserts Cal Bewicke, CEO, Ethical Naturals Inc. (San Anselmo, CA). Bewicke’s company has been selling its L-theanine ingredient, AlphaWave, for about four years. “Demand has been high,” Bewicke says, “and grows consistently for each brand that carries the product.” Describing the ingredient’s effects as “uniquely experiential,” Bewicke says AlphaWave is mainly sold as a standalone supplement, but a number of companies are currently beginning to research and develop it for beverages. “It’s ideal for this use,” he adds, “because it is fully water-soluble and taste-free.”

He adds that the company this past May announced the completion of a randomized, double-blind, placebo-controlled (small and not yet published) study with 20 human subjects, “revealing the stress-reduction effects” of AlphaWave, as well as its usefulness for reducing fatigue and anxiety.

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Ashwagandha
Attracting greater recognition in the United States in recent months, the botanical ashwagandha is an Ayurvedic adaptogen “revered for its ability to revitalize the body and support overall health,” says Bruce Abedon, PhD, vice president of scientific and regulatory affairs, NutraGenesis (Brattleboro, VT). NutraGenesis markets Sensoril, a standardized extract of the ashwagandha root and leaf that first launched in 2002 marketed for stress relief. Since then, demand has increased annually, Abedon reports, with supplement brands including it in general stress-reduction formulations as well as condition-specific formulations, including those for improved cognition, fatigue reduction, improved sleep, and even cardiovascular and joint health. 

A 60-day, double-blind, placebo-controlled human clinical trial(9) with 98 subjects showed that those taking 125 mg of Sensoril daily experienced “significant reductions in stress and sleeplessness,” Abedon says. “There was also a significant reduction in cortisol levels in these subjects during the study, indicating that a primary mechanism of action for Sensoril is that it addresses cortisol in the body,” he adds.

References:
9. 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,” Journal of the American Nutraceutical Association, vol. 11, no. 1 (2008): 50-56 

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Milk-Protein Hydrolysate
Derived from casein, a dairy protein, Pharmachem’s Lactium ingredient appears to be effective in combatting symptoms of stress and “burnout,” as well as improving sleep duration and efficiency, “especially in those individuals with a moderate anxiety or depression profile,” reports Mitch Skop, senior director of new product development, Pharmachem Laboratories (Kearny, NJ). 

“One study looked at the anti-stress efficacy of Lactium on women who considered themselves suffering from stress,” Skop explains. The researchers leading the double-blind, 30-day crossover study of 63 female subjects concluded that “those receiving Lactium reported a significantly greater improvement in stress symptoms versus placebo in the following areas: digestive, intellectual, social, cardiovascular, and emotional.”(10)

More recently, in a double-blind, randomized, placebo-controlled (but small) study published in the Journal of International Medical Research in 2014, a supplement formula containing Lactium “helped significantly decrease symptoms of burnout,” Skop says.(11)

References:
10. Kim JH et al., “Efficacy of S-1 casein hydrolysate on stress-related symptoms in women,” European Journal of Clinical Nutrition, vol. 61, no. 4 (2006): 536-541
11. Jacquet A et al., “Burnout: evaluation of the efficacy and tolerability of TARGET 1 for professional fatigue syndrome (burnout),” Journal of International Medical Research. Published online October 2014. 

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Melatonin
Melatonin, the only hormone supplement sold without a prescription in the United States, has become ubiquitous in brick-and-mortar drug stores, natural/health-food stores, and grocery stores, as well as online. Barely on any American’s radar 15 years ago, the sleep supplement’s popularity and buzz has exploded in recent years, and it is now sold under numerous brands and in a wide variety of forms, including pills, gummies, quick-dissolve tablets, time-release tablets, and-most recently from Natrol (Chatsworth, CA), said to be the top-selling melatonin brand in the United States-liquid concentrate. 

Just how fast has melatonin’s popularity grown? According to a National Health Interview Survey(12) published in 2015, providing comprehensive information on the use of complementary health approaches in the United States and conducted by the National Center for Health Statistics (part of the Centers for Disease Control and Prevention), melatonin use among adults in the United States more than doubled between 2007 and 2012. What’s more, 0.7% of U.S. children (419,000) used melatonin supplements in 2012-a significant increase over the 0.1% of children who used them in 2007. In fact, for American children, the increase of the use of melatonin supplements from 2007 to 2012 was second only to the increase in the use of fish oil/omega-3 fatty acids for the same population.

As for melatonin’s safety and effectiveness, Michael Grandner, PhD, assistant professor of Psychiatry, Psychology, and Medicine, and director, Sleep & Health Research Program, University of Arizona College of Medicine, calls melatonin supplements “quite safe, especially compared with sleeping medications.” However, the United States “may be the only developed country in which melatonin is sold as a supplement without a prescription,” he adds. 

And supplemental melatonin can be effective: Grandner explains, “It nudges the hands on your internal clock a little bit.” Taking melatonin an hour or two before bed, when one’s natural melatonin levels are low but rising, will shift that clock forward somewhat and induce drowsiness sooner than normal.

References:
12. National Health Interview Survey. “Most Used Natural Products.” 2015. https://nccih.nih.gov/research/statistics/NHIS/2012/natural-products/melatonin

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