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Functional beverages can be a valuable component of the human diet with the ability to not only provide essential hydration but to deliver important bioactive compounds that can contribute to chronic disease treatment and prevention. One area of the functional beverage market that has seen an increase in demand in recent years are beverages that promote relaxation and sleep. Sleep is an essential biological process, with optimal sleep being defined as one of adequate duration, quality and timing. It is regulated by a number of neurotransmitters which are, in turn, regulated by dietary intake of essential bioactive compounds.
sleep
nutraceuticals
theanine
chamomile extract
tryptophan
cysteine
functional beverages
1. Introduction
Beverages play an important role in human health and nutrition, not only from the perspective of hydration, but also as mediators of social and cultural connectedness. They can also serve as a source of essential nutrients, particularly for people who may not consume a balanced diet [1]. Beverages are also becoming increasingly popular carriers for the development of functional food products. The last few decades have seen increasing awareness and emphasis on the importance of nutrition for overall health [2]. In addition, busy lifestyles, an aging population and rising healthcare costs in most developed countries have fueled demand for functional food products, particularly beverages [3][4]. These products may contain naturally derived bioactive compounds that can be used to potentially treat and prevent a range of chronic illnesses in addition to optimizing general health [4][5][6].
A substantial body of evidence exists on the health-protective benefits of specific dietary patterns rich in antioxidants and polyphenols, most notably the Mediterranean diet [7][8]. In addition, traditional medicine is now widely accepted in modern medicine as consumers seek more ‘natural remedies’ to treat and prevent illness [9]. In Indian Ayurvedic medicine, for example, Ashwagandha root, is used to treat a range of brain disorders including, anxiety, depression, Alzheimer’s disease, Parkinson’s disease, Schizophrenia and bipolar disorder [10]; Malkangani oil or Jyothishmati oil, obtained from Celastrus paniculatus, provides neuromodulatory, anti-oxidant, anti-inflammatory and sedative properties, among others [11]; Nardostachys jatamansi provides numerous beneficial properties by acting as an anticonvulsant, neuro-protective, hepatoprotective, neuroprotective and hypotensive [12]; and Terminalia arjuna which is used for angina, hypertension, congestive heart failure and dyslipidemia [13].
These dietary patterns and the integration of traditional medicine have led to the research and development of bioactive compounds originating from plant, fungi and animal sources, representing an innovative and fast-emerging area of the food industry [14][15]. Advancement in extraction technologies and refinement of isolation and purification techniques has given rise to specifically formulated products with relatively high purity of selective ingredients of near pharmaceutical standards, providing the amalgamation of nutritional and pharmaceutical products jointly identified as nutraceuticals [15][16][17]. Whilst consumption of a number of supplements in the form of tablets, powders and extracts to improve health is widely accepted, the benefit of a functional beverage is the ability to deliver one or several nutraceutical compounds in one product [18]. Additional benefits include their convenience, storage capabilities, size and flavor variabilities, acceptability and relatively low cost [19]. Some successful commercial examples of the functional beverage concept include sports drinks, ready to drink teas, energy drinks and vitamin-enriched water [20]. These beverages are often designed to improve hydration, concentration and endurance; and delivery of essential vitamins, minerals and polyphenols [4][18]. One area of the commercial health and wellness market which has seen an increase in demand are functional beverages to improve sleep quality [21].
Sleep is essential for wide ranging physiological processes including growth, cognition, immune function, metabolism and cardiovascular health [22][23]. Optimal sleep comprises adequate duration, quality and timing that is regulated by several neurotransmitters including glutamate, acetylcholine, dopamine, serotonin, norepinephrine, histamine, orexin, gamma-aminobutyric acid (GABA), adenosine, melatonin and melanin-concentrating hormone, among others [24]. Some of these compounds are also important in mood, cognition, appetite, behavior and stress [25]. A bidirectional relationship exists between sleep disruption and physiological state, that is influenced by a number of different modalities (Figure 1), and an alteration in neurotransmitter levels can result in sleep disruption, fatigue, impaired performance and impaired memory [26][27][28]. Furthermore, chronic sleep disruption is associated with an increased risk of cognitive decline and memory impairment [27][29], metabolic syndrome (MetS) [30], anxiety and depression [31], type 2 diabetes mellitus (T2DM) [32], cardiovascular disease (CVD) [33], inflammation and infection [34].
Figure 1. Factors Affecting Sleep Quality.
In support of the bidirectional relationship between diet and sleep, macronutrients have also been found to influence sleep quality. A review by St. Onge et al. (2016) reported that a high carbohydrate diet can negatively affect sleep quality by reducing slow-wave sleep and increasing rapid eye movement sleep (REM) [35]. Whereas, a high protein diet can positively effect sleep quality by reducing sleep onset latency and the number of wake episodes during the night [35]. Analysis of data from the National Health and Nutrition Survey (NHANES) conducted in the USA (n = 26,211) has also found that micronutrient deficiencies are inversely associated with sleep duration [36]. Furthermore, adherence to diets that are rich in fish, fruits, vegetables and nuts, such as the Mediterranean diet, have been found to be associated with better sleep quality, including better sleep efficiency and reduced sleep disturbances [37][38]. These diets are rich sources of important compounds involved in the sleep-wake cycle such as L-tryptophan, melatonin, magnesium and vitamin B6, among others, which have been the subject of numerous intervention studies to improve sleep quality [37][38][39]. These compounds are now being included in commercially available functional relaxation or sleep beverages.
2. Active Compounds
The summary of active compounds included here is presented in Table 1. The range of compounds is comprised of amino acid, hormone, vitamin and mineral compounds that influence the neurological pathways involved in sleep with potential for development into a functional beverage.
Table 1. Selected nutraceuticals used in the promotion and improvement of quality of sleep and their outcomes in different population groups.
Note: L-TRP-L-Tryptophan; A-LAC–alpha-lactalbumin; EEG–Electroencephalography; 5-HTP–5-hydroxytryptophan; SWS–Slow Wave Sleep; REM–Rapid Eye Movement; NREM–Non-Rapid Eye Movement; ADHD–Attention Deficit Hyperactivity Disorder; GAD–Generalized Anxiety Dissorder; TG–Treatment Group; PG–Placebo Group; PSQI–Pittsburgh Sleep Quality Index; ICU–Intensive Care Unit; ESS–Epworth Sleepiness Scale; FSS–Fatigue Severity Scale; ISI–Insomnia Severity Index; VAS–Visual Analogue Scale; Astx-Astaxanthin.
3. Nutraceuticals as Potential Targets for the Development of a Functional Beverage for Improving Sleep Quality
The researchers have indicated that L-TRP and melatonin may effectively improve sleep quality, as expected, due to their central roles in the sleep-wake cycle and the extensive studies conducted on these compounds. While the evidence is still relatively limited, micronutrients and 5-HTP may also be effective as functional ingredients due to their important roles in modulating the neurotransmitters of the sleep-wake cycle, particularly serotonin and melatonin. Another finding of this research is the association between inflammation and oxidative stress on sleep quality. Oxidative stress leads to overexcitation of glutamate, decreasing L-CYS uptake. This also activates the kynurenine pathway, redirecting L-TRP and reducing sleep quality [66]. The use of compounds with antioxidant properties, such as L-THE, NAC and vitamins C and D may also be effective in improving sleep quality by reducing oxidative stress. In addition, the researchers have presented the supporting evidence on the effectiveness of traditional sleep promoting beverages, however these findings require further investigation in well-designed clinical trials. In many cases, particularly for the herbal varieties, an extract in the form of a capsule was used to evaluate its effectiveness, and thus the same effect may not be achieved through usual daily consumption of the beverage.
Given the common physiological pathways of the compounds presented here, preliminary data suggests nutraceutical combinations could be effective in improving sleep quality through either a synergistic or enhancing effect. This was evident from the studies looking at the effect of a melatonin/magnesium/B vitamin complex combination, and a melatonin/magnesium/zinc combination.
The future directions for development of functional beverages to improve sleep quality must consider several factors to ensure its claims of functionality are substantiated. The bioavailability and functionality of the nutraceutical compound within the beverage may be affected by dose, solubility, pH, possible interactions with the beverage matrix and other nutraceutical compounds, digestion and gut microbiota following consumption [67][68]. Melatonin, for example, has a bioavailability of approximately 15% following consumption of 2 mg and 4 mg [69]. Whereas L-THE is reported to have a bioavailability of approximately 45%–54% following digestion [70]. The mechanism of action of the nutraceutical and its interaction with other drugs is also important to consider as it may interfere with the action of the drug. For example, magnesium supplementation and the absorption of calcium channel blockers. It may enhance the effect of a drug resulting in an adverse reaction, such as L-TRP supplementation potentially increasing peripheral serotonin in conjunction with SSRI’s. Furthermore, herbal extracts, which can contain over 100 bioactive constituents, may reduce the effectiveness of other nutraceuticals due to chemical interactions. Processing and preserving the beverage and the stability of the nutraceutical compounds within the beverage during storage may also affect their bioavailability [68]. These compounds may need microencapsulation, whereby a compound is encapsulated in a food-grade, biodegradable shell to protect its bioavailability and shelf life [71]. Vitamin C is susceptible to degradation during food preservation [72], whereas L-THE is stable in acidic environments, can withstand high temperatures and has been found to have a long shelf-life [73]. Additionally, a sensory profile of the beverage is essential to ensure its likeability. NAC is reported to have a pungent taste and smell due to its sulfur groups and would therefore require additional flavors and delivery to make it more palatable [74]. The volume of the beverage must also be considered as an increased propensity to urinate after consuming the drink may disrupt normal sleep. Furthermore, when assessing the effectiveness of the beverage, the use of objective sleep assessments such as actigraphy, used in combination with subjective sleep diaries and questionnaires, and a food diary will offer a more comprehensive assessment of efficacy.
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