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Glycine has a calming effect on the brain – it helps you wind down and prepare for sleep – its role as an inhibitory neurotransmitter has been unfolding over many years of ongoing research efforts. Easily one of the most versatile amino acids, glycine serves as a building block to proteins (collagen, the most abundant protein in our body, is one-third glycine), and is heavily utilized for the production of heme, DNA and RNA synthesis, glutathione formation, and for enriching the body’s capacity for methylation reactions [1] [2]. Sleep Problems People need sleep. It is our basic human need. Too many of us experience sleep problems. Laying there restless, counting sheep, watching the hostile glow of the green numbers, fearing the absence of sleep – this dreaded scenario of sleep-deprived desperation is all too familiar. Needless to say, sleep issues have become a pervasive health problem, and research shows that lack of sleep affects everything from mental competence to increased risk of chronic diseases and cancer.

Glycine Promotes Sleep Without Altering Sleep Architecture

When human volunteers who have continuously experienced unsatisfactory sleep were given 3 g glycine before bedtime, their sleep improved [3]. Using polysomnography, a type of diagnostic tool in sleep studies, glycine was shown to shorten the amount of time to fall asleep and stabilize sleep state, with no alterations in sleep architecture, unlike with traditional hypnotic drugs. Glycine promoted normal nocturnal sleep cycles, from deeper to shallower with very few interruptions.

Glycine Lowers Core Body Temperature

So what is it about this tiny amino acid that could be so powerful in contributing to regulating such a complex process as sleep? First of all, glycine taken orally has easy access to the brain – it readily crosses the blood brain barrier via glycine transporters [4].Once in the brain, glycine targets glutamate NMDA receptors in the suprachiasmatic nucleus (SCN) – the 24-hour biological clock in the central nervous system that controls when we want to be asleep and awake. By modulating NMDA receptors in the SCN, glycine induces vasodilation throughout the body to promote lowering of core body temperature [5]. Sleep and body temperature are intertwined – in its circadian oscillation, body temperature decreases before the onset of sleep and continues to decrease throughout the night, reaching its nadir about 2 hours after sleep onset, and gradually rising as a person wakes [6]. Temperature is just one of many 24-hour rhythms our bodies experience throughout the day and as nighttime approaches – the drop is important for initiating sleep. Glycine’s effect on thermoregulation is similar to that of common prescription sleep medications that also work by reducing core body temperature to promote sleep [7] [8].

Unlike many sleep aids out there, nutraceutical or pharmaceutical, that promote sleep and leave you groggy the next day, glycine actually corrects feelings of fatigue and sleepiness during the day.

Additional mechanisms that glycine may rely on to promote sleep include inhibiting orexin neurons – the “wakefulness” neurons (the absence of which is implied in narcolepsy) [9]. However, more research is needed to fully elucidate this process.

Glycine Improves Daytime Performance

Here’s the exciting part – unlike many sleep aids out there, nutraceutical or pharmaceutical, that promote sleep and leave you groggy the next day, glycine actually corrects feelings of fatigue and sleepiness during the day [10]. Sleep-restricted volunteers receiving glycine, after waking, showed improved reaction times in in the psychomotor vigilance test compared to the placebo group and reported feeling refreshed.

Glycine Regulates Daytime Wakefulness

Glycine was found to contribute to yet another circadian process – stimulating the expression of arginine vasopressin – a neuropeptide produced in the SCN. Animal studies show that the expression levels of arginine vasopressin were increased during the day in the glycine treatment group [10]. Arginine vasopressin serves as an output signal of the hypothalamic biological clock, an important modulator of circadian processes involving the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes and the autonomic nervous system [11]. Specifically to the HPA axis, arginine vasopressin synergizes signaling with corticotropin releasing hormone (CRH) to facilitate the release of adrenocorticotropic hormone (ACTH) to ultimately trigger the production of cortisol from the adrenal glands, thus contributing to the state of wakefulness [12]. Sleep isn’t just a time to rest. It’s an active process of cleaning out toxins and repairing brain cells damaged by free radicals [13]. Think about sleep as a form of neural sanitization – during sleep, waste products of brain metabolic processes are removed from the tiny spaces between brain cells where they can accumulate [14]. Sleep, therefore, is a kind of a power cleanse that restores and rejuvenates our brain for optimal function [15]. Considering glycine’s prominent role in detoxifications processes, as future research studies unfold, it would be exciting to see what additional processes glycine helps regulate to support a healthy brain.

References

[1] M.A. Razak, P.S. Begum, B. Viswanath, S. Rajagopal, Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review, Oxid Med Cell Longev 2017 (2017) 1716701.Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine A Review [2] M.F. McCarty, J.H. O’Keefe, J.J. DiNicolantonio, Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection, Ochsner J 18(1) (2018) 81-87.Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection. [3] W.I. Yamadera, K.; Chiba, S.; Bannai, M.; Takahashi, M., Nakayama, K., Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes, Sleep and Biological Rhythms 5 (2007).Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes [4] A. Kurolap, A. Armbruster, T. Hershkovitz, K. Hauf, A. Mory, T. Paperna, E. Hannappel, G. Tal, Y. Nijem, E. Sella, M. Mahajnah, A. Ilivitzki, D. Hershkovitz, N. Ekhilevitch, H. Mandel, V. Eulenburg, H.N. Baris, Loss of Glycine Transporter 1 Causes a Subtype of Glycine Encephalopathy with Arthrogryposis and Mildly Elevated Cerebrospinal Fluid Glycine, Am J Hum Genet 99(5) (2016) 1172-1180. [5] N. Kawai, N. Sakai, M. Okuro, S. Karakawa, Y. Tsuneyoshi, N. Kawasaki, T. Takeda, M. Bannai, S. Nishino, The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus, Neuropsychopharmacology 40(6) (2015) 1405-16.The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. [6] M. Bannai, N. Kawai, New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep, J Pharmacol Sci 118(2) (2012) 145-8.New Therapeutic Strategy for Amino Acid Medicine – glycine improves sleep [7] R.R. Markwald, T.L. Lee-Chiong, T.M. Burke, J.A. Snider, K.P. Wright, Jr., Effects of the melatonin MT-1/MT-2 agonist ramelteon on daytime body temperature and sleep, Sleep 33(6) (2010) 825-31. [8] E.E. Elliot, J.M. White, The acute effects of zolpidem compared to diazepam and lorazepam using radiotelemetry, Neuropharmacology 40(5) (2001) 717-21. [9] M. Hondo, N. Furutani, M. Yamasaki, M. Watanabe, T. Sakurai, Orexin neurons receive glycinergic innervations, PLoS One 6(9) (2011) e25076. [10] M. Bannai, N. Kawai, K. Ono, K. Nakahara, N. Murakami, The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers, Front Neurol 3 (2012) 61.The Effects of Glycine on Subjective Daytime Performance in Partially Sleep-Restricted Healthy Volunteers [11] A. Kalsbeek, E. Fliers, M.A. Hofman, D.F. Swaab, R.M. Buijs, Vasopressin and the output of the hypothalamic biological clock, J Neuroendocrinol 22(5) (2010) 362-72. [12] H.K. Caldwell, E.A. Aulino, K.M. Rodriguez, S.K. Witchey, A.M. Yaw, Social Context, Stress, Neuropsychiatric Disorders, and the Vasopressin 1b Receptor, Front Neurosci 11 (2017) 567.Social Context, Stress, Neuropsychiatric Disorders, and the Vasopressin 1b Receptor. [13] A.R. Eugene, J. Masiak, The Neuroprotective Aspects of Sleep, MEDtube Sci 3(1) (2015) 35-40.Sleep Facilitates Clearance of Metabolites from the Brain [14] L. Xie, H. Kang, Q. Xu, M.J. Chen, Y. Liao, M. Thiyagarajan, J. O’Donnell, D.J. Christensen, C. Nicholson, J.J. Iliff, T. Takano, R. Deane, M. Nedergaard, Sleep Drives Metabolite Clearance from the Adult Brain, Science 342(6156) (10/18/2013) 373-377. [15] A.R. Mendelsohn, J.W. Larrick, Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases, Rejuvenation Res 16(6) (2013) 518-23.   __________________________________________________________________________________________

NUTRITIONAL INTERVENTIONS TO help sleep

KEY POINTS • Given the importance of sleep for optimal health and performance, a number of nutritional interventions has been investigated to determine their effectiveness in enhancing sleep quality and quantity. • As some nutritional interventions may exert effects on neurotransmitters that are involved in the sleep-wake cycle, it is possible that these interventions may enhance sleep. • High glycemic index foods may be beneficial for improving sleep if consumed more than 1 h prior to bedtime and solid meals may be better than liquid meals at enhancing sleep. • From the current literature, it appears that diets high in carbohydrate may result in shorter sleep latencies, while diets high in protein may result in improved sleep quality and diets high in fat may negatively influence total sleep time. • Tryptophan, melatonin and valerian are other substances that have some scientific evidence for enhancing sleep. BACKGROUND While the exact function of sleep is not fully understood, sleep has extremely important biological functions. This is demonstrated by the negative effects that sleep deprivation can have on performance, learning, memory, cognition, pain perception, immunity, inflammation, glucose metabolism and neuroendocrine function. A number of nutritional substances have traditionally been associated with promoting sleep. Researchers have recently begun to investigate their effectiveness as a substitute for pharmacological interventions. SLEEP OVERVIEW Sleep Stages Sleep can be defined as a reversible behavioural state where an individual is perceptually disengaged from and unresponsive to the environment (Carskadon & Dement, 2011). Sleep is a complex physiological and behavioural state that has two basic states based on physiological parameters. These are rapid eye movement (REM) and non-REM (NREM). An electroencephalogram (EEG), in which electrodes measures brain electrical activity, is used to identify the two states (Figure 1). NREM sleep is divided into four stages (1- 4) which are associated with a progressive increase in the depth of sleep (Carskadon & Dement, 2011). REM sleep is characterised by muscle atonia, bursts of rapid eye movement and dreaming. Therefore, REM sleep is an activated brain in a paralysed body. Measuring Sleep There are two commonly used methods to assess sleep. The first is actigraphy and it involves monitors on the wrist, which are worn like a wristwatch that continuously record body movement (usually stored in 1-min periods), and the recording of sleep diaries, where participants record the start and end times and dates for all sleep periods (i.e., nighttime sleeps and daytime naps). Data from sleep diaries and activity monitors are used to determine when participants are awake and when they are asleep. Essentially, all time is scored as awake unless (i) the sleep diary indicates that the participant was lying down attempting to sleep and (ii) the activity counts from the monitor are sufficiently low to indicate that the participant was immobile. When these two conditions are satisfied simultaneously, time is scored as sleep. Actigraphy is useful for understanding sleep patterns as it is noninvasive and relatively easy to collect data over significant periods of time (commonly 2 wk of monitoring). Figure 1. The progression of sleep stages across a single night in a normal young adult volunteer is illustrated in this sleep histogram. The text describes the ideal or average pattern (Carskadon & Dement, 2011). The second method is polysomnography (PSG), by which body functions such as brain activity (EEG), eye movements (EOG), muscle activity (EMG) and cardiac activity (ECG) are measured. PSG provides information on sleep staging and is considered the “gold standard” for assessing sleep quality and quantity. PSG can be expensive, is labour intensive and is often used primarily for assessing clinical sleep disorders. NUTRITIONAL INTERVENTIONS TO ENHANCE SLEEP There are a number of neurotransmitters in the brain that are involved in the sleep-wake cycle. These include serotonin, gammaaminobutyric acid (GABA), orexin, melanin-concentrating hormone, cholinergic, galanin, noradrenaline and histamine (Saper et al., 2005). Therefore, it is possible that nutritional interventions that act upon these neurotransmitters in the brain may also influence sleep. Dietary precursors can influence the rate of synthesis and function of a small number of neurotransmitters, including serotonin (Silber & Schmitt, 2010). Figure 2 below depicts the means by which diet may influence the central nervous system and through the production of serotonin (5-HT) and melatonin. Synthesis of 5-HT is dependent on the availability of its precursor in the brain, the amino acid L-tryptophan (Trp). Trp is transported across the bloodbrain barrier by a system that shares other transporters including a number of large neutral amino acids (LNAA). Thus, the ratio of Trp/ LNAA in the blood is crucial to the transport of Trp into the brain and an increase in this ratio can be achieved by the intake of pure tryptophan or tryptophan-rich protein (Silber & Schmitt, 2010). The food protein with the highest Trp content and most favourable Trp:LNAA ratio is α-lactalbumin, a whey-derived protein (Heine, 1999). Ingestion of other forms of protein generally decrease the uptake of Trp into the brain, as Trp is the least abundant amino acid and, therefore, other LNAA are preferentially transported into the brain. Carbohydrate, however, increases brain Trp via insulin stimulation of LNAA into skeletal muscle, which results in an increase in free-Trp (Fernstrom & Wurtman, 1971). Carbohydrate A small number of studies have investigated the effects of carbohydrate (CHO) ingestion on indices of sleep quality and quantity. Porter and Horne (1981) provided six male subjects with either a high CHO meal (130 g), a low CHO meal (47 g) or a meal containing no CHO, 45 min prior to bedtime. The high CHO meal resulted in increased REM sleep, decreased light sleep and wakefulness (Porter & Horne, 1981). However, the caloric content of the meals was not matched in this study making it impossible to tell whether the effect was due to the carbohydrate or the calories. The effect of meal vs. drink (with high, normal and low CHO contents) vs. water at various time intervals prior to sleep has also been studied (Orr et al, 1997). Results demonstrated that solid meals enhanced sleep onset latency (time taken to fall asleep) up to 3 h after ingestion and the liquid meal was slightly better than water. There was no effect of meal or drink composition on sleep. From this study, it cannot be concluded that the observed effects are an effect of carbohydrate or energy. Afaghi et al. (2007, 2008) conducted two studies investigating CHO ingestion prior to sleep in healthy males. In the first study, high or low Glycemic Index (GI) meals were given 4 h or 1 h prior to sleep (Afaghi et al., 2007). The high GI meal significantly improved sleep onset latency over that of the low GI meal. In addition, providing the meal at 4 h prior to sleep was better than a meal at 1 h prior to sleep. In the second study, a very low CHO meal (1% CHO, 61% fat, 38% protein) was compared to a control meal (72% CHO, 12.5% fat, 15.5% protein) matched for energy, 4 h prior to sleep (Afaghi et al., 2008). The very low CHO meal increased the percentage of time spent in slow wave sleep (stages 3 and 4 of NREM), and the time spent in REM sleep when compared to the control condition. Finally, Jalilolghadr et al. (2011) provided eight children with either a high GI (200 mL milk and glucose) or lower GI drink (200 mL milk and honey), 1 h prior to bedtime. In this study, the high GI drink increased arousal to a greater extent than the low GI drink, suggesting a poorer quality of sleep. From the limited and somewhat contradictory nature of the above studies, it appears that high GI foods may be beneficial if consumed more than 1 h prior to bedtime, and that solid meals may be better than liquid meals at enhancing sleep. Sports Science Exchange (2013) Vol. 26, No. 116, 1-5 3 Acute Mixed Composition Meals Only a small number of studies have investigated the effects of meals or drinks of varying composition on sleep. Hartmann et al. (1979) provided a drink with the evening meal which was either high fat (90 g), high CHO (223 g) or high protein (30 g). The findings revealed no effect of any of the drinks on sleep when compared to no drink. Zammit et al. (1995) examined the effects of high vs. low energy liquid meals (993.5 vs. 306 Kcal) provided at lunch, compared to no meal on daytime naps. Both liquid meals demonstrated increased time in stages 2 and 3 of NREM sleep when compared to no meal. However, there were no differences in sleep onset latency (Zammit et al., 1995). Again, there is very limited research in this area, but it appears that reduced caloric intake may result in poor sleep. Habitual Diet The above-mentioned studies have examined acute nutritional manipulations on sleep. There has also been research conducted that investigated chronic manipulations or habitual dietary intake. Kwan et al. (1986) provided six healthy females with a low CHO (50 g/day) diet for 7 d and reported increased REM latency when compared to sleep prior to the 7 d intervention when the subjects consumed their usual diet. Lacey et al. (1978) also studied females for 7 d with either high protein (>100 g), low protein (<15 g) or normal daily protein intakes. Results showed that high protein intakes resulted in increased restlessness, while low protein intakes resulted in reduced amounts of slow wave sleep. However, there were no differences in total sleep time (Lacey et al., 1978). While it is difficult to draw definitive conclusions from this study, it is clear that altering daily protein intake may affect sleep quality. In a recent comprehensive study, Lindseth et al. (2011) manipulated the diet of 44 adults for 4 d. Diets were either high protein (56% protein, 22% CHO, 22% fat), high CHO (22% protein, 56% CHO, 22% fat) or high fat (22% protein, 22% CHO, 56% fat). Diets higher in CHO resulted in shorter sleep onset latencies and diets higher in protein resulted in fewer wake episodes. There was little effect of the high fat diet on markers of sleep quality and quantity (Lindseth et al., 2011). Finally, Grandner et al. (2010) examined the dietary intake (through questionnaires) of 459 postmenopausal women over 7 d. The only significant finding of this study was that fat intake was negatively associated with total sleep time (Grandner et al., 2010). From the above studies, it appears that diets high in carbohydrate may result in shorter sleep latencies, while diets high in protein may result in improved sleep quality and diets high in fat may negatively influence total sleep time. However, additional research is necessary in this area. Tryptophan As mentioned above, the synthesis of 5-HT in the brain is dependent on the availability of its precursor Trp. Further, 5-HT is a precursor to melatonin in the pineal gland (Silber & Schmitt, 2010). There have been numerous studies investigating the effects of tryptophan supplementation on sleep (for review, see Silber & Schmitt, 2010) and it appears that doses of Trp as low as 1 g can improve sleep latency and subjective sleep quality. This can be achieved by consuming ~300 g of turkey or ~200 g of pumpkin seeds. Melatonin Melatonin is a hormone that is associated with circadian rhythms (Morin & Benca, 2012) and some research has demonstrated sedative/hypnotic effects of this compound (Buscemi et al., 2005). However, research investigating the use of melatonin for primary insomnia demonstrates inconclusive results (Morin & Benca, 2012). A meta-analysis reported a reduction in sleep onset latency of 7.2 min and concluded that while melatonin appeared safe for short-term use, there was no evidence that melatonin was effective for most primary sleep disorders (Buscemi et al., 2005). Another recently investigated intervention is tart cherry juice. Tart cherries contain high concentrations of melatonin and when consumed over a 2 wk period improved subjective insomnia symptoms when compared to placebo (Pigeon et al., 2010). There have also been reports of modest improvements in sleep time and quality (Howatson et al., 2011). Valerian Valerian is an herb that binds to GABA type A receptors and is thought to induce a general calming effect on the body (Wheatley, 2005). Results of a meta-analysis showed subjective improvement in sleep quality, but not quantity (Fernandez-San-Martin et al., 2010). Other Nutritional Interventions Nucleotides are believed to be involved in the physiological function of sleep, in particular uridine monophosphate (5’UMP) and adenosine monophosphate (5’AMP). 5’UMP causes a depressive effect on the central nervous system and one study that administered low doses prior to sleep reported improvements in some sleep indices (Chagoya de Sanchez et al., 1996). 5’AMP has hypnotic properties and levels of this nucleotide decline during wakefulness (Sanchez et al., 2009). 5’AMP acts on the adenosine A2A receptors in the venterolateral nuclei region of the brain, which is believed to be related to insomnia, pain and depression (Cubero et al., 2009). These nucleotides have been studied via investigations regarding the possible hypnotic effects of infant formula (Sanchez et al., 2009). In this study, the sleep-promoting formula contained high levels of L-tryptophan and carbohydrates, low levels of protein, and 5’UMP and 5’AMP. Fiftyfour children were monitored over 1 wk using actigraphy, with results showing increased time in bed and increased sleep efficiency. Sports Science Exchange (2013) Vol. 26, No. 116, 1-5 4 The authors suggested that these results supported the concept of chrononutrition, i.e., the influence of time of day at which food is ingested having effects on different biological rhythms, such as sleep and wakefulness. However, no blood measures were made and thus it was not possible to determine whether the ingested compounds were transported from the digestive system to the bloodstream and which of the ingredients were actively involved in enhancing sleep. Glycine (a non-essential amino acid) functions as an inhibitory neurotransmitter in the central nervous system and also acts as a co-agonist of glutamate receptors. Glycine has been shown to improve subjective sleep in a recent Japanese study (Bannai et al., 2012). Yamadera et al. (2007) also reported shorter sleep onset latencies measured by polysomnography (“gold standard” for sleep assessment). The authors speculated from previous studies on rodents that potential mechanisms may involve increased vasodilation and thus lowering of core temperature, and increased extracellular serotonin release in the prefrontal cortex of the brain (Yamadera et al., 2007). L-theanine is an amino acid analogue present in tea but not coffee that demonstrates pharmacological actions such as promoting feelings of calmness and reduced alertness. One study reported that L-theanine partially counteracted the caffeine-induced decrease in slow wave sleep in rats (Jang et al., 2012). There are also numerous other traditional products that are purported sleep aids including passionflower, kava, St. John’s wort, lysine, magnesium, lavender, skullcap, lemon balm, magnolia bark, 5-HTP and GABA. While the majority of these products have not been adequately investigated in the scientific literature, many can be found in sleep aid supplements that can be purchased over-the-counter in pharmacies and health food suppliers. However, like many available supplements, there is always the danger that these purported sleep aids may contain illegal substances and thus should be used with caution. PRACTICAL APPLICATIONS Athletes should focus on utilising good sleep hygiene to maximise sleep (See previous Sports Science Exchange article on “Sleep in Elite Athletes”). While research is minimal and somewhat inconclusive, several practical recommendations may be suggested: • High glycemic index (GI) foods such as white rice, pasta, bread and potatoes may promote sleep. However, they should be consumed more than one hour prior to bedtime. • Diets high in carbohydrate may result in shorter sleep latencies. • Diets high in protein may result in improved sleep quality. • Diets high in fat may negatively influence total sleep time. • When total caloric intake is decreased, sleep quality may be disturbed. • Small doses of tryptophan (1 g) may improve both sleep latency and sleep quality. This can be achieved by consuming ~300 g of turkey or ~200 g of pumpkin seeds. • The hormone melatonin and foods that have a high melatonin concentration may decrease sleep onset time. • Subjective sleep quality may be improved with the ingestion of the herb valerian. SUMMARY While the quantity of research investigating the effects of nutritional interventions on sleep is increasing, future research needs to highlight the importance of nutritional and dietary interventions to enhance sleep both in the general population and in athletes. Careful examination of both the timing of food ingestion and the use of different interventions would provide invaluable information to athletes on how to improve sleep through nutritional means. Ideally, research will lead to nutritional interventions for optimising both sleep quality and quantity, as well as enhancing athlete recovery from training and competition. Sports Science Exchange (2013) Vol. 26, No. 116, 1-5 5 REFERENCES Afaghi, A., H. O’Connor, and C.M. Chow (2007). High-glycemic-index carbohydrate meals shorten sleep onset. Am. J. Clin. Nutr. 85:426-430. Afaghi, A., H. O’Connor, and C.M. Chow (2008). Acute effects of the very low carbohydrate diet on sleep indices. Nutr. Neurosi. 11:146-154. Bannai, M., N. Kawai, K. Ono, K. Nakahara, and N. Murakami (2012). The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Front. Neurol. 3: 61. Buscemi, N., B. Vandermeer, N. Hooton, R. Pandya, L. Tjosvold, L. Hartling, G. Baker, T. P. Klassen, and S. Vohra (2005). The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J. Gen. Intern. Med. 20:1151-1158. Carskadon, M.A., and W.C. Dement (2011). Normal human sleep: an overview. In: M.H. Kryger, T. Roth and W.C. Dement (eds.) Principles and Practice of Sleep Medicine. St Louis: Elsevier, pp. 16-26. Chagoya de Sanchez, V., R. Hernandez-Munoz, J. Suarez, S. Vidrio, L. Yanez, R. Aguilar-Roblero, A. Oksenberg, A. Vega-Gonzalez, L. Villalobos, L. Rosenthal, F. Fernandez-Cancino, R. Drucker-Colin, and M. Diaz-Munoz (1996). Temporal variations of adenosine metabolism in human blood. Chronobiol. Int. 13:163-77. Cubero, J., B. Chanclon, S. Sanchez, M. Rivero, A. B. Rodriguez, and C. Barriga (2009). Improving the quality of infant sleep through the inclusion at supper of cereals enriched with tryptophan, adenosine-5’-phosphate, and uridine-5’- phosphate. Nutr. Neurosci. 12:272-80. Fernandez-San-Martin, M.I., R. Masa-Font, L. Palacios-Soler, P. Sancho-Gomez, C. Calbo-Caldentey, and G. Flores-Mateo (2010). Effectiveness of Valerian on insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Med. 11:505-511. Fernstrom, J.D., and R.J. Wurtman (1971). Brain serotonin content: physiological dependence on plasma tryptophan levels. Science 173:149-152. Grandner, M.A., D.F. Kripke, N. Naidoo, and R.D. Langer (2010). Relationships among dietary nutrients and subjective sleep, objective sleep, and napping in women. Sleep Med. 11:180-184. Grimmett, A., and M.N. Sillence (2005). Calmatives for the excitable horse: a review of L-tryptophan. Vet. J. 170:24-32. Hartmann, M.K., A.H. Crisp, G. Evans, M.K. Gaitonde, and B.R. Kirkwood (1979). Short-term effects of CHO, fat and protein loads on total tryptophan/tyrosine levels in plasma as related to %REM sleep. Waking Sleeping 3:63-68. Heine, W.E. (1999). The significance of tryptophan in infant nutrition. Adv. Exp. Med. Biol. 467:705-710. Howatson, G., P.G. Bell, J. Tallent, B. Middleton, M.P. McHugh, and J. Ellis (2011). Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. Eur. J. Nutr. 51:909-916. Jalilolghadr, S., A. Afaghi, H. O’Connor, and C.M. Chow (2011). Effect of low and high glycaemic index drink on sleep pattern in children. J. Pak. Med. Assoc. 61:533-536. Jang, H.S., J.Y. Jung, I.S. Jang, K.H. Jang, S.H. Kim, J.H. Ha, K. Suk, and M. G. Lee (2012). L-theanine partially counteracts caffeine-induced sleep disturbances in rats. Pharmacol. Biochem. Behav. 101:217-221. Kwan, R.M., S. Thomas, and M.A. Mir (1986). Effects of a low carbohydrate isoenergetic diet on sleep behavior and pulmonary functions in healthy female adult humans. J. Nutr. 116: 2393-2402. Lacey, J.H., C. Hawkins, and A.H. Crisp (1978). Effects of dietary protein on sleep E.E.G. in normal subjects. Adv. Biosci. 21:245-247. Lindseth, G., P. Lindseth, and M. Thompson (2011). Nutritional effects on sleep. West. J. Nurs. Res. 2011 Aug 4. [Epub ahead of print]. Morin, C.M. and R. Benca (2012). Chronic insomnia. Lancet 379:1129-1141. Orr, W.C., G. Shadid, M.J. Harnish, and S. Elsenbruch (1997). Meal composition and its effect on postprandial sleepiness. Physiol. Behav. 62:709-712. Pigeon, W.R., M. Carr, C. Gorman, and M.L. Perlis (2010). Effects of a tart cherry juice beverage on the sleep of older adults with insomnia: a pilot study. J. Med. Food 13:579-583. Porter, J.M., and J.A. Horne (1981). Bed-time food supplements and sleep: effects of different carbohydrate levels. Electroencephalogr. Clin. Neurophysiol. 51:426-433. Sanchez, C. ., J. Cubero, J. Sanchez, B. Chanclon, M. Rivero, A.B. Rodriguez, and C. Barriga (2009). The possible role of human milk nucleotides as sleep inducers. Nutr. Neurosci. 12:2-8. Saper, C.B., T.E. Scammell, and J. Lu (2005). Hypothalamic regulation of sleep and circadian rhythms. Nature 437:1257-1263. Silber, B.Y. and J.A. Schmitt (2010). Effects of tryptophan loading on human cognition, mood, and sleep. Neurosci. Biobehav. Rev. 34:387-407. Wheatley, D. (2005). Medicinal plants for insomnia: a review of their pharmacology, efficacy and tolerability. J. Psychopharmacol. 19:414-421. Yamadera, W., K. Inagawa, S. Chiba, M. Bannai, M. Takahashi, and K. Nakayama (2007). Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep Biol. Rhythms 5:126-131. Zammit, G.K., A. Kolevzon, M. Fauci, R. Shindledecker, and S. Ackerman (1995). Postprandial sleep in healthy men. Sleep 18:229-231. ______________________________________________

Sleep in Elite Athletes and Nutritional Interventions to Enhance sleep

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BOTANICALS FOR A BETTER SLEEP

iStock-963914130Imagine waking up fully rested, ready to tackle any challenge and embrace all the pleasures of the world with gratitude. We all know what a good night’s sleep feels like, but how often do we get it? In this hectic, hyper-stimulated, nerve-wracking world, it is challenging to create a sleep routine that our bodies and brains need to function optimally. Good sleep hygiene and use of natural herbs and botanicals can help promote a healthy amount of sleep. The result could mean an improvement in problem solving and work performance, weight management, and prevention of chronic disease such as diabetes, depression and cardiovascular disease. There are multitudes of products and advice in this arena of sleep. An article from 2016 suggested Americans spent over $41 billion on sleep remedies, with an expected increase to upwards of $52 billion by the year 2020. How much sleep do we really need? As you might expect, children require more sleep than adults. The average child needs up to 11 hours of sleep per night, while most adults should get 7-8 hours. According to the Center for Disease Control, the average American gets 6.8 hours. Collectively, we’re not reaching the minimal sleep requirement of 7 hours, and sleep deprivation represents one of the top behaviors deleteriously affecting our overall health. Many factors contribute to this deficit: work schedules, family obligations, and chronic illness or behavioral issues. In most of these cases, our circadian rhythms are completely out of whack. What are some natural remedies or botanicals to help promote sleep? The regulatory body internationally recognized for its comprehensive data on medicinal herbs, the German Commission E, recommends common botanicals (valerian, lavender, lemon balm, and hops) to help support relaxation and promote sleep. There are other popular choices that have sedative qualities, such as passion flower, chamomile, and kava kava. Most of these relaxant botanicals can be found commonly in teas, but they are also available in supplement form. Almost always found in blends, these herbs all have various mechanisms of action, and, therefore, act synergistically when combined. Valerian (Valeriana officinalis) affects sleep by interacting with neurotransmitters GABA, adenosine and serotonin. A two-week randomized controlled trial study comparing the common sleep aid zolpidem (Ambien) with a blend of valerian, passion flower and hops found no statistically significant difference in overall sleep quality. The root or rhizome of this plant is used in either teas or processed into an extract for use in supplements. The extract is standardized to its valerenic acid content, usually containing 0.3-0.8% of the constituent. Doses in supplements are typically 150-600 mg. Use of valerian generally requires about 2 weeks before it appears effective, but studies have been limited to 4-6 weeks, so use beyond that time frame should be approached with caution. Lavender (Lavandula angustifolia) is an extremely popular floral herb found in essential oil form, teas, extracts and in other botanical blends to promote relaxation and relieve stress. Recent research has identified it functions by antagonizing NMDA-receptors and serotonin transporters.  Doses of 80 mg per day lavender in gel cap form for up to 10 weeks have been used in a study where subjects had unspecified anxiety. Both quality and duration of sleep improved in those participants with no sedative side-effects as found in pharmaceutical sleep remedies. Other uses of lavender include 1-2 teaspoons in hot water as a tea daily, or its essential oil diluted in a carrier oil used for massage or in a warm bath. Lavender is generally safe, however it has been known to be toxic if ingested orally. Lemon balm (Melissa officinalis) has ancient roots as an antiviral and stomach-calming agent as well as a treatment for sleep disorders caused by nervousness or tension. Studies have shown the mechanism of action of lemon balm may be related to interactions with GABA-A receptors. Hops (Humulus lupulus), besides having a super fun Latin name and serving as the main ingredient in many beers, is one of the herbs commonly found blended in teas or supplements to produce a calming effect. Researchers have not completely elucidated exactly how hops produces this effect, but it has been shown to bind to serotonin and melatonin receptors. Valerian-hops combination products have been the most widely studied in placebo-controlled, double-blind randomized controlled trials comparing them to benzodiazepine-class sleep medications with varying results. Like lemon balm, evidence for its use as an herbal treatment for relaxation or insomnia has a rich history in tradition. Passionflower (Passiflora incarnata) is another botanical used to address anxiety and insomnia. Researchers have found passionflower functions by increasing levels of GABA, producing a relaxation effect. In a Japanese study from 2017, scientists found passionflower extract modulated the levels of the neurotransmitters and the genetic expression of the related enzymes in vivo and in vitro. This resulted in positive effects on circadian rhythms. Sleep Hygiene Tips Dr. Michael Polsky, a board-certified sleep physician, recommends considering sleep hygiene for improving sleep. Sleep hygiene is a term used to describe how we prepare our minds and bodies for sleep, beginning hours before actual anticipated sleep. In fact, the window of 2-3 hours prior to sleeping turns out to be quite important. Here are some tips for keeping good sleep hygiene:

  • At least 2-3 hours prior to sleep, have a light, balanced dinner and minimize liquids
  • Make a plan to abstain from electronic devices 1-2 hours prior to sleep
  • Do some light activity such as walking or yoga; avoid a hard workout or any activity that is too stimulating
  • Reduce or eliminate caffeine (from coffee, tea, chocolate) in the diet; or no more than 1-2 cups of coffee or tea before lunch
  • Keep a regular sleep schedule, even on weekends

A simple tea recipe Mix up a batch of 2 parts peppermint leaf, 1 part lemon balm, 1 part passionflower, 1 part lavender. Steep one heaping teaspoon in a teacup of hot water for 5 minutes and enjoy as a relaxing beverage. Phenitropic sleep aid link VHP Mix for insomnia _______________________________________________________________

Applications for α-lactalbumin in human nutrition

α-Lactalbumin is a whey protein that constitutes approximately 22% of the proteins in human milk and approximately 3.5% of those in bovine milk. Within the mammary gland, α-lactalbumin plays a central role in milk production as part of the lactose synthase complex required for lactose formation, which drives milk volume. It is an important source of bioactive peptides and essential amino acids, including tryptophan, lysine, branched-chain amino acids, and sulfur-containing amino acids, all of which are crucial for infant nutrition. α-Lactalbumin contributes to infant development, and the commercial availability of α-lactalbumin allows infant formulas to be reformulated to have a reduced protein content. Likewise, because of its physical characteristics, which include water solubility and heat stability, α-lactalbumin has the potential to be added to food products as a supplemental protein. It also has potential as a nutritional supplement to support neurological function and sleep in adults, owing to its unique tryptophan content. Other components of α-lactalbumin that may have usefulness in nutritional supplements include the branched-chain amino acid leucine, which promotes protein accretion in skeletal muscle, and bioactive peptides, which possess prebiotic and antibacterial properties.

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Sleep Facilitates Clearance of Metabolites from the Brain b

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