Ingredients for sleep support have taken off with product sales in this category posting strong double-digit growth.

The panel:

Michael Chernyak, President, CK Nutraceuticals, Oakville, ON, Canada, https://ckingredients.com

Julia Diaz, Head of Marketing, Pharmactive, Madrid, Spain, http://pharmactive.eu/en/home-en/

Kim Edwards, Global Product Manager, Kemin Human Nutrition and Health, Des Moines, IA, www.kemin.com

Mariko Hill, Product Development Executive, Gencor, Hong Kong, https://gencorpacific.com

Mark LeDoux, Chairman and Chief Executive Officer, Natural Alternatives International, Carlsbad, CA, www.nai-online.com

Thomas Li, Business Development Manager, IFF Health, Ridgefield, NJ, https://iff-health.com

Dan Lifton, President, Maypro Ventures, Purchase, NY, www.maypro.com

Shoji Matsukawa, Vice President, Mitsubishi Gas Chemical America, New York, NY, http://mgc-a.com

Eric Meppem, Commercial Director/Co-Founder, Pharmako, New South Wales, Australia, http://pharmako.com.au

Seventy to 80 million Americans suffer from a slew of sleep problems, with anxiety issues plaguing 40 million people. According to the American Psychological Association, nearly half of Americans believe that their stress levels have increased over the past five years.

As we might expect, the COVID-19 pandemic has only made things worse.

According to the Kaiser Family Foundation, more than 33.3 percent of adults in the U.S. have reported persistent anxiety during the pandemic. By comparison, in the same period of time, in 2019, only one in 10 (11 percent) adults reported regular feelings of anxiety.

Fortunately, the natural products industry has come a long way from the earliest examples of sleep-support products. In researching this article, NIE came across a print ad from 1939 for a product called “CHEER,” a health drink “made from seeds” which promised to make consumers to “sleep like a top” and “wake up feeling like a lark,” in addition to banishing blues and nixing nervousness.

While claims like this from the early decades of the modern health-food industry may seem comical or cringe-worthy to brand marketers today, it does show that consumers, even back then, were seeking products to sleep better and relax more easily.

Today, there’s a wide range of somewhat more sophisticated and science-backed ingredients and formulas for sleep and relaxation support, and our expert panel takes a look at the newest solutions and opportunities in this category.

NIE: What is the state of the market for natural ingredients and products for relaxation and sleep, especially in light of the pandemic?

Matsukawa: The American Sleep Apnea Association estimates that up to 70 million Americans of all ages experience sleep-related problems. While sleeplessness or sleep disorders can occur for a variety of reasons, stress and anxiety can compound the situation.

Whether it’s a global pandemic, the general political climate, or the current financial crisis, Americans have a lot on their mind. As a result, it’s understandable that many are finding it difficult to get quality sleep. According to a 2019 market study by Kline, the U.S. sleep aid market has seen a significant boom, with natural ingredients and products for relaxation and sleep expected to grow at a double-digit rate.

Li: [Due] to the COVID-19 situation, the expected growth for the sleep supplements [category] may reach 30 percent growth in 2020. Increased anxiety, less physical movement due to quarantine have all contributed to sleep issues. While melatonin is a mainstay for the market, consumers are constantly looking for more natural alternatives.

Lifton: Sales of supplements in the sleep category have been booming—posting double-digit growth, as high as over 12 percent by one estimate. That, coupled with the fact that stress is reported to be a serious problem for at least 50 percent of people, manufacturers have an opportunity to make a real difference in the health and quality-of-life of American consumers.

Hill: In light of an unprecedented global pandemic, it seems only plausible that the [market focus] is on immunity and cognitive health. However, even before the pandemic, the mood/relaxing supplement was a booming category that grew at a CAGR (compound annual growth rate) of 5.7 percent in 2014-2019, reaching 1.3 billion EUR in 2019 (Euromonitor’s Health and Nutrition Survey, Jan & Feb 2020). Similarly, [other] data show that sales in the sleep category are outpacing those in the supplement market as a whole.

Before COVID gripped the world in a chokehold, there was a steady increase in the demand for stress relieving and sleep-promoting products. In fact, Pre-COVID, according to Euromonitor, about 50 percent of the world’s consumers claimed to be suffering from some level of stress.

Diaz: From our standpoint, natural sleep aids—and those which promote relaxation and positive mood—are rapidly growing categories in the supplement sector. People increasingly view a healthy lifestyle and good sleep as something inextricably linked, and they gravitate towards natural botanicals.

LeDoux: The market for supplements dealing with enhancing sleep for people is burgeoning to say the least. With the advent of the economic disruption caused by the coronavirus and the various government mandates initiating lockdowns and restrictions on travel and some semblance of normalcy, people are being challenged as never before. As such, with the concerns about economic welfare, family activities, employment and travel restrictions—the amount of anxiety being initiated by these often-ill-conceived restrictions is at a significant level.

Chernyak: The pandemic has not left anyone unscathed—all consumer demographics and segments are dealing with unprecedented uncertainty amid COVID-19, and this has led to increased levels of stress as well as sleep disruptions—an inability for many to rest their minds, day and night.

NIE: Which ingredients for sleep and relaxation support have stood the test of time and what new ones have emerged?

Chernyak: One of the emerging stars in sleep and stress categories is ashwagandha—I am very impressed with what Ixoreal Biomed has done with their KSM-66 ingredient. The investment Ixoreal has made in high-quality scientific research is truly admirable. Another ingredient with great potential for mood support (a close relative of stress and sleep, and equally important, in our view) is saffron extract. There are some excellent published papers on its mood-balancing effects.

Matsukawa: Research into pyrroloquinoline quinone (PQQ), a compound known to stimulate mitochondria and support cognitive performance, has shown it has a wide range of health benefits, including working as a mood enhancer and helping to increase sleep.

In fact, Mitsubishi Gas Chemical Company has studied this ingredient extensively and developed a natural source of PQQ, which it brands under the name BioPQQ.

In one particular open-label study, BioPQQ demonstrated positive effects on stress, fatigue and sleep. Test subjects who took 20 mg of BioPQQ daily for eight weeks saw significant improvements in vigor, fatigue, tension-anxiety, depression, anger-hostility and confusion. Additionally, measures for quality of life, appetite, sleep, obsession and pain also improved considerably among both male and female subjects during this same period of time. The BioPQQ study revealed improvement in drowsiness at awakening, sleep onset and maintenance, and sleep duration as well.

BioPQQ is made in Japan through a natural fermentation process and is the only ingredient of its kind to receive a New Dietary Ingredient (NDI) no-objection letter from the FDA (U.S. Food and Drug Administration).

Hill: Melatonin’s growth rate has been well above category rates for some time and is accelerating. Melatonin is now the second-largest segment behind probiotics in the Vitamin, Mineral and Supplement sector.

As far as newer entrants, palmitoylethanolamide (PEA) not only has clinically proven success in reducing pain and inflammation but Gencor’s PEA—Levagen+ study also suggested the supplement helps reduce anxiety as well as improve sleep quality.

PEA can help promote restful sleep through activation of CB1 receptors, which increases a calming effect inducing sleep. It can also increase restful REM sleep […] by activating TRPV1 channels.

PEA activates energy-boosting, fat-burning, and anti-inflammatory PPAR alpha. By activating this key protein, PEA stops the activity of pro-inflammatory genes and the production of many inflammatory substances.

PEA reduces the activity of the bliss gene, FAAH, that breaks down natural cannabinoid anandamide. This increases the levels of calming anandamide in your body, helping to combat pain and increase relaxation. It may also activate cannabinoid receptors (CB2 and CB1).

Diaz: Some [sleep-supportive] botanicals have a deep-rooted history as traditional, natural agents that can safely relieve anxiety and promote rest. However, in some cases, these botanicals work too generally to promote mental balance, and often only work in large doses.

Pharmactive offers a very effective branded saffron extract named affron. affron is derived from saffron that is hand-picked from Pharmactive’s own private fields in Castille-La-Mancha. affron has been standardized to a higher concentration of Lepticrosalides, the compound responsible for the positive effect on mental health that can induce rest and better sleep. affron is further backed by multiple clinical trials.

Lifton: There are a few unique proprietary extracts that have emerged which have a very strong basis in science. One of these that we offer is ETAS, a special enzyme-processed asparagus stem extract that has a proven ability to reduce stress and improve sleep.

Another research-validated proprietary extract we offer is Venetron, a new dietary supplement ingredient for sleep, mood and stress support, one without the concerns associated with standard St. John’s wort, kava or 5-HTP.

The right melatonin ingredient is equally important. Dissolution studies show that time-release MicroActive Melatonin delivers 40 percent of its dose at one hour, a gradual release of 50 percent of the remaining dose over the next five hours, and 10 percent after seven hours. This makes it perfect for falling asleep, staying asleep and preventing early awakening. By comparison, pure melatonin was shown to have an initial release of 90 percent of the dose, and to release the remaining 10 percent over the next three hours.

NIE: In a related question, what research on relaxation and sleep ingredients are manufacturers and suppliers interested in?

Matsukawa: Supplement manufacturers are looking for ingredients that can increase the quantity and quality of mitochondria, because this powerhouse of our cells is responsible for regulating cognitive function, memory, energy and mood.

Research has shown that bad mitochondria can result in more active oxygen, which can cause stress and fatigue. However, good mitochondria can enhance better sleep, which in turn allows a person to generate more good mitochondria.

As a result, consumers can benefit from supplements that contain natural mitochondrial boosting ingredients because they can help to create healthy mitochondria, which play a critical role in improving one’s quality of life. Various studies have revealed BioPQQ can increase and enhance mitochondrial biogenesis, even outperforming other well-known mitochondria enhancers by 500 to 1,000 times.

NIE: What are the latest developments in proprietary ingredients, delivery technologies and applications for sleep and/or relaxation support?

Li: As consumers become more educated, proprietary blends are becoming more of a thing of the past, as there is higher demand for full efficacious doses. While much of the supplement industry is moving toward non-pill formats, the sleep category is lagging a bit in terms of innovation. Most non-pill formats are around gummies and shots, along with traditional teas, but there is increased innovation around multi-phase delivery (similar to caffeine), where the product may help consumers sleep through the night and not require them to take multiple doses.

Meppem: Pharmako Bitoechnologies specializes in delivery technologies. In particular, relevance to sleep/relaxation support ingredients—we have two different technologies currently on the market. The first is LipiSperse, which is our patented, award-winning dispersion technology. This allows lipophilic particles to be disperse in water or the gastrointestinal tract. This has two profound effects: (1) improving bioavailability, proven in human pharmacokinetic studies: and (2) enhancing functionality, allowing use in novel dosage formats. Examples of LipiSperse formulations include Levagen+ and HydroCurc.

The second is Pharmako’s CPOs or Compressible Powdered Oils technology. Compressible Powdered Oils (CPOs) are an innovative material development which allows oily active ingredients to be included in tablet and powder formulations without leaching oil. The technology allows oily active ingredients to become compressible powders suitable for tableting and ready-to-mix formulations. They offer better shelf stability than oils, with less sensitivity to air and oxidation and allow some materials to be included together that were previously incompatible.

Hill: Pharmactive applies a proprietary green extraction technology called AFF ON Cool-Tech to safeguard the potent actives of saffron, one of the earth’s most highly valued and fragile botanicals. This eco-friendly technique ensures the highest possible concentration of actives using no harmful solvents, synthetics or additives of any kind. It generates low waste and considerably reduces the impact on the environment, minimizing the company’s carbon footprint. It also requires less industrial processing and less energy consumption in fewer steps.

Chernyak: As I mentioned, KSM-66 is a rising star, but also gaining significant market traction with our proprietary SaffSerene ingredient, a standardized saffron extract supported by well-designed human clinical studies demonstrating effectiveness in balancing mood.

LeDoux: With the advent of all kinds of products using cannabidiols, it would appear that some older formulations have been dusted off for revisiting in a new formulary utilizing CBD extracts in tinctures or other quasi-ingestables (which have their own legal jeopardy) for presentation to the American consumer. While there is some good anecdotal observations regarding benefits to alleviating anxiety with CBD, the method of ingestion remains legally questionable given the FDA’s perspective on the category.

NIE: In a related question, it appears that there may be more of a focus on supporting health areas that are the underlying factors as to why certain customers sleep poorly, such as urinary health. Please discuss.

Meppem: Two major reasons for lack of sleep (or poor quality sleep) are stress/anxiety and pain. Reducing anxiety or stress helps improve quality of sleep. Another common reason for poor sleep is pain. This can be muscular, nerve or joint pain. New studies are looking at how alleviating these symptoms then also improves sleep.

Li: There is a direct link between urinary issues and less sleep, and this also related to age and gender. If we have to wake up several times each night to go to the restroom, it does not help our sleep. In addition, when we become older we can fall sleep easily but then struggle to stay asleep.

IFF Health has two ingredients for urinary incontinence, Go-Less (for women) and Go-Less (for men) which is clinically backed to show an increased quality of life as participants were able to sleep better with less [urinary] frequency through the night.

Lifton: While we can’t solve all problems via supplementation, we can address many functional areas that were not amenable to nutritional targeting until recently. For example, we know that chronic and acute stress negatively impact cognition, including memory and reasoning. Research has shown that our ETAS ingredient can help with both.

In one study, participants who took 300 mg of ETAS daily for three weeks had three times the levels of heat shock protein HSP70 released, which is important since HSP protects our cells from stress-caused damage. Other research found stress response improvements in the autonomic nervous system in people who took ETAS.

Getting enough sleep is vital for optimal cognitive functioning, too. Healthy males who took ETAS showed an 80 percent reduction in cortisol levels and 2.5 times less expression of the psychological stress marker, chromogranin A, leading to better sleep.

Diaz: Consumers and formulators are increasingly aware that achieving optimal well-being is about targeting the root of the problem, but the underlying factors are something very specific to each individual.

A good example is urinary health. It has been reported that frequent urination during the night negatively impacts sleep quality and, thus, affects overall health-related quality of life. Waking numerous times a night can seriously reduce resting hours and, as a result, affect the sleep cycle completion. This is especially important in aging consumers.

In this context, affron targets key brain mechanisms that play a major role in stress, emotional well-being and even aging. These include the balance of neurotransmitters (such as serotonin), stress signals, and anti-inflammatory and antioxidant effects.

NIE: How can manufacturers of finished products select and utilize the right mix of proprietary branded ingredients (PBIs) and commodity ingredients to create unique formulations that offer end users the most bang for their buck?

Meppem: Choosing ingredients with proper clinical research is very important. Including these at the correct dose leads to improved efficacy. Efficacious products means better consumer compliance and repeat sales. Consumers and retailers look for two things: products which have potential to sell regularly and novel products. Novel products lead to increased consumer trial new users in the category. The most successful recent launches of novel formulations also provide consumers with convenience.

Pharmako has worked with many customers in markets all around the world to help create unique formulations which are efficacious and convenient (easier to take).

Lifton: The right mix of proprietary and commodity ingredients is important for effective formulas that provide value which consumers appreciate. A flagship proprietary ingredient in a finished product should be selected based on how that ingredient drives the efficacy of the formulation, not based on any window-dressing considerations. Once your product is anchored with the right PBI at the right dose—and supported by human clinical research—then other complementary commodity ingredients can be selected based on how well all the ingredients combine together to create a good product that has a unique selling proposition.

Hill: Unique combinations of ingredients, ones which ensure that consumers are getting multiple benefits are becoming more necessary if manufacturers are to stay in the game.

Not only using ingredients that offer multiple benefits but using ingredients that are synergistic and work well together. Keeping the dosage of supplements correct to ensure effectiveness and using innovative delivery systems, like LipiSperse, to ensure maximum absorption of the ingredients is a sure way to deliver smart and suitable formulations to consumers.

NIE: What’s one burning question about this category that you wanted to be asked, and what’s your response to that question?

Hill: I would like to respond to this question: “How effective is CBD in improving sleep quality and what clinical research backs these statements?”

CBD has gained a lot of interest in the past two years due to its purported “sleep benefits” through acting on the endocannabinoid system. However, all of these claims are based on anecdotal evidence. No single double-blind, randomized, placebo-controlled trials on a healthy human population has been published on the benefits of CBD on sleep.

When it comes to alternatives, PEA is an ingredient that acts on similar pathways as CBD. PEA is an endogenous fatty acid amide that increases levels of anandamide, an endocannabinoid that regulates pain and sleep receptors. By having this indirect influence, as well as direct mechanisms on PPAR-a for anti-inflammatory properties, many CBD companies have started to consider use of PEA as a safe and legal alternative.

Li: I would think manufacturers would ask, “How do I know which of the same ingredient to pick from?” For manufacturers, the key is to look at the active levels to make sure you’re not sourcing a watered down version of the ingredient or from an ineffective part of the plant.

Take chamomile for example, which should be standardized to apigenin. Apigenin is the key active responsible for a variety of benefits, notably inducing muscle relaxation and sedation for sleep support. Otherwise, consumers could be ingesting other parts of the plant that are not contributing toward the effect they are looking for.

Diaz: I would like to respond to, “What do you consider are the key essential principles in manufacturing and marketing natural herbal supplements?

Pharmactive places science and transparency at the top of its agenda in order to achieve full customer confidence and trust in our products. Our extractions are 100 percent natural and they are standardized by HPLC technology to ensure the highest purity and concentration of the ingredient. Our company oversees the entire supply channel. We work closely with our farmers and have set in place a robust quality control system. We have acquired several quality seals, including organic certification, to ensure that it is in line with customer values for quality and traceability of naturally sourced ingredients.

Meppem: I would respond to, “What is the consumer insight that brands should focus on relating to sleep?”

The key insight is that consumers can feel when a product works in relation to sleep. Don’t be too clever, formulate with ingredients supported by clinical research, and use the correct dose. Giving a consumer a product that works will lead to success. NIE

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