Month: April 2017

When is the Best Time to Take Your Muscle Memory?

Muscle Memory is a cutting edge arginine supplement, created from many years of science research. Little do many of us know though, is that the science isn’t just in the nutrient itself. We think, “Okay I have a new supplement, I just need to make sure I take it everyday,”–this usually ends up being first thing in the morning or right before bed for most people. This actually isn’t the correct logic when it comes to Muscle Memory consumption.

According to our Scientists-Designer Foods Creators, Durk Pearson and Sandy Shaw, Muscle Memory is best absorbed when taken on an empty stomach. Arginine acts as a growth hormone releaser, and when taken orally, this amino acid should be taken at least 45 minutes before consuming food. When amino acids are consumed, either by food sources or supplement sources, they must transport across our brain’s  blood barrier to initiate their physiological processes. These amino acids, which are in many foods, have to essentially compete to gain transport across the blood brain barrier. When you take Muscle Memory with a meal, the arginine that you are supplementing may not access passage across the barrier because there are many other amino acids as a result from consuming a meal. By isolating the intake of arginine, this ensures that passage occurs and the growth hormone (also referred to as GH) release process, that has many anti-aging properties, occurs properly.

As aging occurs, the release of GH becomes more and more limited. A few G
H release benefits include:

  • Accelerated wound healing
  • Ability to maintain strength gain
  • Improvement of skin elasticity
  • Improved immune support
  • Muscular strength
  • Kidney health
  • Relief of musculoskeletal aches and pains

The idea behind Muscle Memory is to prolong  the high spikes of GH release that we experience in our younger years. Muscle Memory isn’t a GH supplement, bWoman Sipping Coffee While on Bedut the arginine, choline, and vitamin B5 in the supplement naturally initiate GH’s release and all of the body’s regulatory features and processes that occur around this physiologic mechanism. In order to receive the full benefit of the GH release, Durk and Sandy suggest that Muscle Memory be ta
ken at bedtime because about an hour and a half after you go to sleep is when the biggest GH release occurs if you are older than mid-20s. Additionally, Muscle Memory can be consumed 45 minutes before engaging in peak-output exercise. Mirroring the body’s natural GH release patterns with Muscle Memory use, allows for the best chance of accelerating this overall process and reaping all of the great, anti-aging benefits.

As Durk puts it, “ Muscle Memory makes your endocrine system look like that of a younger person.”


Durk & Sandy Muscle Memory Interview

Why you should take Lift & Muscle Memory on an empty stomach

Productive Sleep

Young woman relaxing in bedLife Priority, Inc. Introduces Durk Pearson & Sandy Shaw’s®


Sleep is far more than a daily period during which you lapse into a lengthy state of unconsciousness. It is a highly programmed mental state that engages all parts of your brain in a complex pattern of activity.  Not a passive resting state, sleep is an active brain state essential for neuronal plasticity, enabling your brain to function more effectively.

When you get a good nights sleep, you awake with a sense of refreshment and well-being, having been prepared for a new day by a night of productive sleep.  But how often does that happen?

Confronted with the dilemma of non-productive sleep, which increases with age, life extension scientists Durk Pearson & Sandy Shaw have found that certain sleep-enhancing natural substances, when formulated, can help make it easier to just let go and slip into nighttime sleep without a struggle, even at the end of or during a day that may be full of hard work and stressful events.

Named Productive Sleep™, Durk & Sandy designed this new formulation for their own persona use because “there are a lot of things to worry about these days and we really need good sleep.”  Furthermore they say, “Productive Sleep™ works for us.  Several of our best friends have reported enthusiastically on the effects of Productive Sleep™.”

Productive Sleep™ is good for daytime naps, when it can also enhance.  New research has reported beneficial effects on cognition (particularly memory) of daytime naps, as well.

And it can work for you too.  After you fall asleep, Productive Sleep™ can help your brain navigate nature’s restorative sleep pathways. Productive Sleep contains several important co-factors that we feel supports better brain health: GlycineGABACholine, Taurine, Theanine.


We call Productive Sleep™, “Time in a Bottle,” because it gives us what we really need, which is time itself.  If sleep becomes more efficient, it can create more productive time every day out of thin air.”  So why wait?  Time is running out!   Try our Productive Sleep™ today and sleep like an angel!

Information provided for educational purposes only. *These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.



By Durk Pearson & Sandy Shaw

GABA, gamma-aminobutyric acid, is a substance naturally found in food,A,B such as tea, that is “strongly implicated in the regulation of sleep, with GABA activity emanating from the ventrolateral preoptic nucleus of the hippocampus dramatically inhibiting wakefulness-associated neurotransmitter activity.”1 “several GABA agents are FDA approved for the treatment of insomnia.”1 “Available evidence for the pathophysiology of insomnia points to a disorder of hyperarousal …”1 Hyperarousal would mean a tendency to remain alert and vigilant, which would seriously interfere with getting to sleep.

Interestingly, in a study1 comparing brain cortical GABA levels (through proton magnetic resonance spectroscopy) in persons with and without primary insomnia, mean occipital GABA levels was 12% higher in those with insomnia as compared to those who had no sleep complaints. The authors suggest that the increased GABA levels may be reflective of a relative “GABA resistance” that resulted in an adaptive increase in GABA levels in those with insomnia. The researchers also found that GABA levels correlated inversely with time awake after sleep onset in persons with primary insomnia and also reported (for the first time, they say) that this relationship is also present in a control group without insomnia. This means that the higher the GABA levels, the less time spent awake after sleep onset in both a group of people with insomnia problems and those without.

The Sleep-Switch Model of GABA Inhibitory Activity in Sleep vs. Arousal

A model was proposed1G to depict the switch from inhibitory to arousal activity in various areas of the brain that regulate sleep vs. waking. It was suggested that the sleep nucleus (VLPO) and the arousal nuclei (TMN, LC, and raphe nuclei) are mutually inhibitory. Thus when the inhibitory drive to the VLPO is high, this reduces the inhibition on the arousal areas, resulting in the wake state. When the inhibitory drive to the VLPO is decreased, the arousal centers are inhibited and sleep occurs. The action of GABA at inhibitory receptors plays a major role in this switch. As noted by the author,1G “GABA(A) receptors are the molecular targets for almost all of the hypnotics approved for the treatment of insomnia.” (Note: this was in 2007.)

As noted in paper #1G, the neurons of the VLPO express the inhibitory transmitters GABA and galanin and project to inhibit the arousal nuclei (TMN, LC, LDT, PPT, PcF, and raphe nuclei.” The VLPO is reported1G to be significantly smaller in elderly humans, which the author suggests may be associated with altered sleep patterns in older individuals, possibly resulting in less sleep and more wakefulness.

GABA Controls the Contribution of Maturing Neurons to the Adult Hippocampal Network

New neurons are continuously generated in the dentate gyrus of the hippocampus throughout life in mammals. This is important for continued learning and formation of new memories. A very recent paper1B reports that the development of GABA inputs onto these adult-born neurons is likely a “significant factor distinguishing young neurons from mature neurons.” As we have written before and is noted in this paper,1B adult-born neurons are more vigorous—exhibiting increased excitability and plasticity—than early-born ones and contribute importantly to several aspects of learning and memory. The experimental data reported in this new paper was summed up: “Combined, these data demonstrate that the unique connectivity of immature GCs [granule cells] affords them a functional role that is different from mature neurons in the DG [dentate gyrus] circuit, a distinction that potentially underlies many of the proposed functions of new neurons in the hippocampal network.” As they further explain, [t]he selective regulation of GABA on the plasticity potential of GCs of different ages is of particular importance in considering how the hippocampal network stores and maintains memories throughout life.”

Another paper1C reported that the presence of GABA(A) receptor deficit in immature neurons of the developing and adult brain “can serve as a common molecular substrate for deficits in adult neurogenesis and behavior indicative of anxious and depressive-like mood states.”

GABA Protection Against Post-Traumatic Stress Disorder

GABA has anti-stress effects. In fact, an earlier paper1D reported that low post-trauma GABA plasma levels was a predictive factor in the development of acute post-traumatic stress disorder (PTSD). The researchers studied 78 road traffic victims on arrival at a traumatology department and assessed them for PTSD 6 weeks later. The same group also evaluated the relationship between post-trauma GABA plasma levels and PTSD at a one year followup.1E As reported in paper #1E, [a]mong patients who met all or nearly all criteria for PTSD at 6 weeks, 75% of those with post-trauma GABA levels above 0.20 mmol/ml no longer met criteria by 1 year. By contrast, among patients whose GABA levels were below 0.20 mmol/ml, 80% met all or nearly all criteria for PTSD at 1 year.”

The researchers1E concluded that “[a] plasma GABA level above 0.20 mmol/ml may protect against chronic PTSD and may represent a marker of recovery from trauma.”

A further paper on the subject of PTSD and GABA1F reports that patients with PTSD have been found to have lighter sleep (more stage 1, less stage 3) and elevated REM density as compared to controls. Moreover, other studies performed by the authors of paper #1F have been said to document an association between fragmented REM sleep with the development of PTSD during the early aftermath of trauma.

The Complexity of GABA is One of Many Substances Involved in Sleep Regulation

As pointed out in another paper,2 GABA is one of many substances that are considered SRS (Sleep Regulatory Substances). The requirements for being an SRS include: “1) the substance and/or its receptor oscillates with sleep propensity; 2) sleep is increased or decreased with administration of the substance; 3) blocking the action or inhibiting the production of the substance changes sleep; 4) disease states, e.g., infection, associated with altered sleep also change levels of the putative SRS; and finally 5) the substance acts on known sleep regulatory circuits.”2

Inflammatory cytokines, such as TNF-alpha and IL-1, are associated with sleep loss and they accumulate with sleep deprivation. Under inflammatory conditions, neurons become more or less sensitive to neurotransmitters and neuromodulators such as adenosine, glutamate and GABA.2 A good summation of the complex stew of which GABA is a part that constitutes the sleep recipe is: “… sleep is an emergent property of populations of local neural networks undergoing state transitions.”2

GABA May Decrease Inflammatory Cytokine Production in Autoimmune Diseases

A recent paper2B reported that GABA modulates inflammatory responses in autoimmune diseases such as the non obese diabetic mouse model of type 1 diabetes and, as found experimentally in this study,2B GABAergic agonists “potently ameliorated” the ongoing paralysis of the EAE multiple sclerosis model in mice by inhibiting inflammatory cytokine production by acting directly on antigen-presenting cells (APC).

GABA Levels in the Pontine Reticular Formation are Greater During Wakefulness than During REM Sleep

One of the complexities of sleep is that the levels of SRS vary depending upon the part of the brain you are looking at as well, of course, as the time of day. In a recent paper,3 scientists found an inverse relationship between changes of GABA and acetylcholine (ACh) during REM sleep in the pontine reticular formation (PRF, a brain area importantly involved in the regulation of sleep and wakefulness). This indicates, the authors believe, that low GABAergic tone combined with high cholinergic tone in the PRF contributes to the generation of REM sleep. This supports the hypothesis that GABA levels in the PRF are greatest during wakefulness and lowest during REM sleep. (This particular study was done in cats.)

In another paper4 in which scientists were also investigating sleep regulation in the pontine reticular formation (this time in rats), they found that concentrations of glutamate and GABA in this brain area varied across the sleep/wake cycle. “Regression analysis revealed that decreases in glutamate and GABA accounted for a significant portion of the variance in the duration of NREM sleep and REM sleep episodes.”4 Thus, the authors note, these data support the hypothesis that endogenous glutamate and GABA in the pontine reticular formation contribute to the regulation of sleep duration. The authors cite a study in which decreasing GABA levels in this brain area by blocking GABA synthesis with 3-mercaptopropionic acid significantly decreased wakefulness and significantly increased NREM sleep and REM sleep.4

GABA, a natural constituent of sleep-wake regulation in the brain, is an important member of getting enough productive sleep.


  1. Chuang et al. Antidepressant effect of GABA-rich monascus-fermented product on forced swimming rat model. J Agric Food Chem. 59:3027-34 (2011).
  2. Zhao et al. Determination and comparison of gamma-aminobutyric acid (GABA) content in Pu-erh and other types of Chinese tea. J Agric Food Chem. 59:3641-8 (2011).
  3. Morgan et al. Cortical GABA levels in primary insomnia. Sleep. 35(6):807-14 (2012).

1B.          Li et al. Development of GABAergic inputs controls the contribution of maturing neurons to the adult hippocampal network. Proc Natl Acad Sci USA. 109(11):4290-5 (2012).

1C.          Earnheart et al. GABAergic control of adult hippocampal neurogenesis in relation to behavior indicative of trait anxiety and depression states. J Neurosci. 27(14):3845-54 (2007).

1D.         Vaiva et al. Low posttrauma GABA plasma levels as a predictive factor in the development of acute posttraumatic stress disorder. Biol Psychiatry. 55:250-4 (2004).

1E.          Valva et al. Relationship between posttrauma GABA plasma levels and PTSD at 1-year follow-up. Am J Psychiatry. 163(8):1446-8 (2006).

1F.          Mellman. A human model that suggests a role for sleep in the cognitive neuropsychology of PTSD and recovery. Sleep. 32(1):9-10 (2009).

1G.         Harrison. Mechanisms of sleep induction by GABA(A) receptor agonists. J Clin Psychiatry. 68[suppl. 5]:6-12 (2007).

  1. Clinton et al. Biochemical regulation of sleep and sleep biomarkers. J Clin Sleep Med. 7(5):Supplement S38-S42 (2011).

2B.          Bhat et al. Inhibitory role for GABA in autoimmune inflammation. Proc Natl Acad Sci USA. 107(6):2580-5 (2010).

  1. Vanini et al. Endogenous GABA levels in the pontine reticular formation are greater during wakefulness than during rapid eye movement sleep. J Neurosci. 31(7):2649-56 (2011).
  2. Watson et al. Sleep duration varies as a function of glutamate and GABA in rat pontine reticular formation. J Neurochem. 118(4):571-80 (2011).


© Copyright Durk Pearson & Sandy Shaw.® All rights reserved.


Information provided for educational purposes only. *These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.

*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.



Productive Sleep doesn’t have to be just a dream.

Introducing Life Priority’s Productive Sleep™
Good sleep doesn’t have to be just a dream.™ Get more power
from your nap!™ Get more out of the sleep you get.™

By Durk Pearson & Sandy Shaw

Hundreds of substances, both natural and synthetic, have been tried over the past few thousand years as sleep-inducing agents. Many were successful in inducing unconsciousness. Why, then, did they generally fail to provide the user with a feeling of rested refreshment the next morning? The answer is complex, but the bottom line is that no one substance can perform the very complex task of helping you to have a more refreshing nap or night’s sleep.

SLEEP is far more than a daily period during which you lapse into a lengthy state of unconsciousness. It is a highly programmed mental state that engages all parts of your brain in a complex pattern of activity. “… sleep is no longer considered a passive resting state, but rather an active brain state essential for neuronal plasticity.”1 If all has gone well, you awake with a sense of refreshment and well-being, having been prepared for a new day by a night of productive sleep.
New research has reported beneficial effects on cognition (particularly memory) of daytime naps, as well.

Our new sleep formulation Productive Sleep is designed to equip your brain with supplies of sleep-enhancing natural substances to help make it easy to just let go and slip into a daytime nap or nighttime sleep without a struggle, even at the end of or during a day that may be full of hard work and stressful events. Then, after you fall asleep, Productive Sleep helps your brain navigate nature’s restorative sleep pathways.
We designed Productive Sleep for our own personal use because there are a lot of things to worry about these days and we really need good sleep. Productive Sleep works for us. Several of our best friends have reported enthusiastically on the effects of Productive Sleep.

1. Lepousez and Liedo. Life and death decision in adult neurogenesis: in praise of napping. Neuron. 71:768-71 (2011).

What Does Good Sleep Do For You Besides Produce a State of Restedness and Energy When You Wake Up?
Underneath the surface of feeling rested and ready to proceed with a new day’s activities is where all the action is, the complex biochemical processes resulting from a night of the right amount of physiological sleep. Not surprisingly, there is much yet to be learned about how sleep works, but some things are becoming much clearer. A major result of sleep is now known to be a process of re-experiencing memories and restoring them into long-term storage.1–4 Another important process involves the creation of new adult-born neurons (neurogenesis)5 that allows two (known) critical brain areas to continue to produce neurons throughout life. These new neurons are particularly important for vigorous youthful function as compared to old early-born neurons.

“… sleep is no longer considered a passive resting state, but rather an active brain state essential for neuronal plasticity.”

 Sleep Preserves Memories
A new study5 along with a commentary on that paper6 reports that the sleepiness that often follows a meal and results in a daytime nap has been found to contribute to synaptic plasticity by …
promoting dampening of potentiated synapses during awake state to minimize their energy consumption, reduce their physical volume, and prevent their strength from saturating. Thus, synaptic depression or downscaling during sleep may recalibrate synaptic weights down to a more responsive range. In parallel to this homeostatic process, sleep has been shown to contribute to memory consolidation. Notably, repeated reactivation of activity patterns evoked during learning [when awake] has been observed during slow-wave sleep both in rats and humans.6
This reactivation is called “replay” and may be essential to the preservation of memories in long-term storage.

“The results suggest that sleep—even as brief as a nap—facilitates the reorganization of discrete memory traces into flexible relational memory networks.”

Improved Reactivation of Information Acquired During the Wake State Via The Power Nap
A new study6A reports on how learning a skill can be improved by an afternoon nap. People learned to produce two melodies in time with moving visual symbols by pressing four keys in time with repeating 12-item sequences of moving circles. Then, when an EEG indicated that a subject was in slow wave sleep during an afternoon nap, one of the melodies was covertly presented 20 times over a 4-minute interval. The performance of the melody presented during the nap (called the cued melody) was found to be played more accurately when the subjects awoke. In subjects who also practiced the two melodies but slept during the afternoon nap without a cued melody, the average playing after awakening improved as well, in correlation with the amount of time spent in slow wave sleep, but not to the degree of improvement shown by those exposed to the cued melody during slow-wave sleep.

“Our [Lau et al, 2011] results make clear that sleep is important for the abstraction of generality.”

The authors explain that prior studies have shown a strengthening of spatial associative memory from learning-related cues presented during slow-wave sleep. Thus, the new study extended the earlier findings by showing that “auditory cues can selectively change the ability to perform a distinct type of sensorimotor skill memory.”6A

The researchers did not test during other stages of sleep, noting that slow wave sleep “has been recognized as being critical for systems memory consolidation.”6A
Another paper6B reported on a daytime nap study in which subjects had to learn the English meanings of Chinese characters with overlapping semantic components called radicals. When they were later tested on new characters that they had never seen before but which shared the same radicals, they had to show that they understood the general concepts represented by the radicals; the participants that took naps, whether they took place immediately after learning or following a delay, performed better. “The results suggest that sleep—even as brief as a nap—facilitates the reorganization of discrete memory traces into flexible relational memory networks.” “Our results make clear that sleep is important for the abstraction of generality.”6B

Sleep and Neurogenesis Part of the neurogenesis process is the production of new neurons, of course, but also the paring of the population of new neurons by controlled death (apoptosis) of some of these newborn cells. This complex process is just beginning to be understood. The new paper5 found that while the apoptosis of newly born neurons is constant over time in mice allowed unlimited access to food, the number of apoptotic neurons is increased strongly after eating when food is restricted to a limited time period (4 hours). Thus, the new neurons are being constantly turned over. However, a postprandial nap (sleep following a meal) also resulted in a potentiation in the rate of apoptosis in the new neurons. This was experimentally shown by preventing the animals from sleeping after a meal, which resulted in the prevention of apoptosis of the newly formed neurons. The regulation of the process of apoptosis is critically dependent upon LEARNING taking place in the newborn neurons, with learning supporting the survival of these neurons. The critical period of learning is 14 to 35 days after cell birth for promotion of survival, while immature (7 to 13 day cells) and cells older than the critical period are not affected.5

“It is only when sensory experience is associated with learning or with postprandial sleep, two processes that involve top-down inputs to the OB [olfactory bulb], that it can affect apoptosis.”6
Interestingly, the process in the olfactory bulb of neuronal birth, apoptosis of some newborn neurons, and the survival of the rest is all a part of the process essential for optimal olfactory exploration and for correct odor discrimination. As the authors of the commentary paper6 explain, during the awake state olfactory experience “tags” a subpopulation of newborn neurons from which a select group will be actively supported to survive during subsequent sleep where they will receive a “reorganizing” signal.

In summation, “sleep is no longer considered a passive resting state, but rather an active brain state essential for neuronal plasticity.”6

1. Maquet et al. Be caught napping: you’re doing more than resting your eyes. Nat Neurosci. 5(7):618-9 (2002).
2. Mednick et al. The restorative effect of naps on perceptual deterioration. Nat Neurosci. 5(7):677-81 (2002).
3. Lau et al. Relational memory: a daytime nap facilitates the abstraction of general concepts. PLoS ONE. 6(11):e27139 (2011).
4. Payne. Sleep on it!: stabilizing and transforming memories during sleep. Nat Neurosci. 14(3):272-4 (2011).
5. Yokoyama et al. Elimination of adult-born neurons in the olfactory bulb is promoted during the postprandial period. Neuron. 71:883-97 (2011).
6. Lepousez and Liedo. Life and death decision in adult neurogenesis: in praise of napping. Neuron. 71:768-71 (2011).
6A. Antony et al. Cued memory reactivation during sleep influences skill learning. Nat Neurosci. 15(8):1114-6 (2012).
6B. Lau et al. Relational memory: a daytime nap facilitates the abstraction of general concepts. PLos ONE. 6(11):e27139 (Nov. 2011).
Reduced Capacity for Sleep With Age
Another paper7 reports differences in sleep capacity with age in a study of 18 older subjects (12 males, 6 females, 60–78 years, mean age 67.8 ± 4.3 years) and 35 younger subjects (17 males, 18 females, 18–32 years, mean age 21.9 ± 3.3 years). All subjects were healthy and had no sleep complaints or sleep disorders.

“Sleep is no longer considered a
passive resting state, but rather
an active brain state essential for
neuronal plasticity.”

The authors report: “Total daily sleep duration, which was initially longer than habitual sleep duration, declined during the [3–7 days of the] experiment to asymptotic values that were 1.5 hr shorter in older (7.4 ± 0.4 SEM, hour) than in younger subjects (8.9 ± 0.4). Rapid-eye-movement sleep contributed about equally to this reduction [in the older subjects].” Thus, the authors concluded that under conditions of sleeping freely (with no conditions of constraint), both daytime sleep propensity and the maximal capacity for sleep are reduced in older subjects, with the obvious implication that older subjects may be more likely to experience insomnia or have other sleep problems. The researchers report studies documenting changes in the quality of sleep across the lifespan that includes decreases in nighttime sleep, polysomnographically assessed reductions in slow wave (NREM sleep stages 3 and 4), and increased daytime sleep. However, as the authors note, the understanding of what these changes mean is limited. For example, if older people need less sleep than younger ones, then less sleep might be appropriate. It is certainly the case that infants need a great deal more sleep than adults do.

  1. Klerman and Dijk. Age-related reduction in the maximal capacity for sleep—implications for insomnia. Curr Biol. 18:1118-23 (2008).

The Sleep-Wake Cycle—Some Facts
The complexity of the sleep wake cycle—what is currently known of it—would be impractical for review here. Instead, we provide some key features of current understanding.
One excellent review8 of the sleep-wake cycle provides the following facts:
(1) There are two basic forms of sleep: slow-wave sleep (SWS) and rapid eye movement (REM) sleep. REM sleep is sometimes called paradoxical sleep because of the atonia (paralysis) of postural muscles along with twitching and episodic bursts of sacchades of quick conjugate eye movements that accompanies it.
Our comment: Although your muscles are normally immobile during REM, you can of course have dreams full of physical action. In some sleep disorders, muscular activity breaks through and can become part of the action during REM, e.g., you can dream you are kicking somebody and wake up to find you have kicked something or somebody.
(2) The review identifies several populations of wake-promoting neurons in the hypothalamus, including those in the basal forebrain, lateral hypothalamus, and tuberomammillary nuclei. Some of these neurons contain acetylcholine, which participates in arousal input to the cerebral cortex during waking. The lateral hypothalamus is identified as a possible “wake switch” that allows the hypothalamus to control the transition from sleep to wakefulness by firing at the start of the transition. Neurotransmitters involved in the waking process include adrenergic, histaminergic, dopaminergic, and cholinergic.
(3) The orexin neuropeptide (also called hypocretin) is an important waking factor. The review mentions that there are only a few thousand neurons in the lateral hypothalamus that express this neuropeptide. The brain disorder narcolepsy, where humans and some animals, such as dogs and even mice, can fall asleep suddenly in the middle of performing an action, is due to a deficiency in orexin. A human autopsy study on narcoleptic individuals was said to show a reduction in the number of orexin-containing cells by 85–95% as compared with normal individuals.8
(4) Natural substances that are involved in the induction and maintenance of sleep include GABA, glycine, acetylcholine (responsible for the muscle atonia during REM, for example), adenosine (caffeine and other methylxanthines are adenosine antagonists, which is one reason they can keep you awake), and certain prostaglandins. Curiously, prostaglandin D2 has been identified as a potent inducer of sleep but is also the prostaglandin released by niacin that causes flushing.
Our comment: The time profile of the release of prostaglandin D2 when inducing sleep may be different from the very short-term effect it has during niacin flushing. We don’t know. Though we both find the niacin flush to induce a transient feeling of well-being, it doesn’t put us to sleep. We do, however, take a dose of niacin at bedtime. Still, it is interesting to note that the drop in core body temperature that occurs at the onset of sleep is associated with increased cutaneous (skin) blood flow. The niacin flush also increases cutaneous blood flow.

  1. Murillo-Rodriguez et al. Mechanisms of sleep-wake cycle modulation. CNS Neurol Disord Drug Targets. 8:245-53 (2009).

Sleep Deprivation Impairs cAMP Signaling in the Hippocampus
Many studies have examined sleep-deprived animals and people to help identify sleep mechanisms and to develop treatments for cognitive problems associated with sleep deficiency.
One recent paper9 identified impaired cAMP (cyclic AMP) signalling in the hippocampus of sleep deprived C57BL/6J male mice (2–5 months of age). cAMP is an important participant in learning and memory including the process called long-term potentiation (LTP) in the hippocampus. The reduced cAMP in the hippocampi of the mice was associated with increased levels of phosphodiesterase-4, an enzyme that degrades cAMP. Thus, the treatment of the mice with a phosphodiesterase-4 inhibitor drug rolipram “rescued” the sleep-deprived deficit in cAMP signalling, synaptic plasticity, and hippocampus-dependent memory. It is interesting to note that phosphodiesterase inhibitors are used in the treatment of many diseases. For example, Viagra is an inhibitor of phosphodiesterase-5, which degrades cGMP that is required for male erection.
The researchers explain that “circadian oscillation of cAMP in the hippocampus has recently been linked to the persistence of memory, so such drugs [phosphodiesterase-4 inhibitors] may also be useful in treating memory deficits associated with alterations in circadian rhythms.” They didn’t mention jet lag, but that is certainly an obvious situation experienced by most, if not all, readers of this publication, in which disruption of circadian rhythms can result in memory deficits.

  1. Vecsey et al. Sleep deprivation impairs cAMP signalling in the hippocampus. Nature. 461:1122-1125 (2009)
    Melatonin May Prevent the Memory Deficits Associated with Total Sleep Deprivation in Rats
    A key sleep-promoting substance is melatonin, produced in and released from the pineal gland. It is known to have effects on circadian rhythms and immune function and to have antioxidative and neuroprotective properties.9
    After total sleep deprivation for five days (using an apparatus that forces the animals to stay awake and in motion in order to avoid being dumped into water), the expression of SIRT1 (sirtuin 1) and COX (cyclooxygenase, which occurs in two forms: COX1 and COX2) were drastically decreased in a recent study.9 SIRT1 is an important regulator of neuronal plasticity and is highly neuroprotective, among other things, and a deficit in its expression can lead to cognitive impairment and oxidative stress.9 SIRT1 is also the famous longevity protein found in studies in some animal models of aging to increase lifespan. The expression of SIRT1 is increased by the equally famous resveratrol, found in red wine, tea, and cocoa.
    During the five days of total sleep deprivation, the experimental rats received either no melatonin or various doses of melatonin (5, 25, 50, or 100 mg/kg of body weight) via intraperitoneal injections once daily. All of the tested doses of melatonin caused a significant increase in the activity of SIRT1 and COX as compared to controls receiving no melatonin. Effects were more significant at the higher doses of melatonin. The animals subject to total sleep deprivation that received no melatonin showed impaired performance in the Morris water maze test. Interestingly, while the animals totally sleep deprived were impaired in finding the hidden platform in the Morris water maze, they took nearly identical lengths of time (compared to the sleep deprived but melatonin treated animals) to reach a visible platform. Thus, the authors conclude, the total sleep deprivation caused a spatial learning deficit rather than causing some sort of sensorimotor disability.
    We have not included melatonin or 5-hydroxytryptophan in this formulation because we wanted the formula to be useful for enhancing short daytime naps. Melatonin, tryptophan, or 5-hydroxytryptophan can be used to very good effect when taken at bedtime.


  1. Hung-Ming Chang et al. Melatonin preserves longevity protein (sirtuin 1) expression in the hippocampus of total sleep-deprived rats. J Pineal Res. 47:211-20 (2009).
    Regulation of Proinflammatory Cytokines by the Circadian Clock Protein Cryptochrome
    A growing number of papers exploring the mechanisms that help explain detrimental effects of sleep disruption or deprivation are being published. Another new one,11 noting the increased susceptibility of people suffering from sleep deprivation to inflammation-associated diseases such as diabetes, obesity, and cancer, led researchers to examine the effects of double knock out (knocking out both CRY1 and CRY2, the genes for CRY, the core clock component protein cryptochrome, in mice and in knockout cells. The bottom line was that “the absence of the core clock component protein cryptochrome (CRY) leads to constitutive elevation of proinflammatory cytokines in a cell-autonomous manner. We observed a constitutive NF-kappaB and protein kinase A (PKA) signalling activation in CRY1-/-; CRY2-/- cells.”11
    As the researchers explain, “secretion of cytokines, TNF-alpha and IL-6 has been reported to display circadian oscillation in macrophages, where ~8% of transcriptome [molecules acting as transcription regulators] is under circadian regulation. Clinical evidence and sleep-loss studies have identified physiological connections between the circadian clock and immune system.”11
    Just another reason to get good restorative sleep!


  1. Narasimamurthy et al. Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines. Proc Natl Acad Sci USA. 109(31):12662-7 (2012)

Toward Better Sleep Quality
We know of no sleep-promoting remedy, including our own, that has actually been tested experimentally for its effects on all these cognitive and emotional processes that have been reported to take place during sleep. Fortunately, you can detect how well you slept by how you feel and perform when you wake up and later during the day. That’s a pretty reliable test for good quality sleep. It also has the great advantage of not requiring you to wait for the FDA to approve anything!

 “If you sleep till noon, you have no right to complain that the days are short.”
— Thomas Fuller, Gnomologia
© Copyright Durk Pearson & Sandy Shaw, 2013

To Your Health!

Life Priority, established in 1994, offers supplements that are scientifically-formulated, results-oriented, and GRAS (Generally Recognized As Safe) and are manufactured at USDA and FDA inspected facilities. rev. 9.3.2013
Information provided for educational purposes only. *These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.


Theanine Neuroprotective, Stress Reducing, Sleep Quality Improver

By Durk Pearson & Sandy Shaw

Theanine was isolated from green tea as a flavor constituent by Sakato in 1949. A 1998 paper (unfortunately in Japanese)3B was said to show that oral intake of L-theanine caused a feeling of relaxation in human volunteers; the study was cited in a 2000 paper.4 The latter paper4 reported on a study that showed that theanine can modulate the stimulating effects of caffeine, thus acting as a relaxant, in 9 week old Wistar rats.T he final ingredient in our Productive Sleep™ is theanine (gamma-glutamylethylamide), an amino acid found in white and green tea. It can pass the blood-brain barrier and, in fact, has been shown to have neuroprotective effects in the brain that include protection against the injury induced by transient forebrain neuronal ischemia,1,2 oxidative stress in the brain,3 reduced brain cell death due to stroke in mice3A and reduced stress induced by a mental arithmetic task in human volunteers.6 (Most people find mental arithmetic very stressful!) We expect that, since theanine protects against transient forebrain neuronal ischemia, it would also provide protection from the reduced brain oxygenation caused by sleep apnea.

In the rat-caffeine study,4 the rats had electrodes implanted in the cortex, hippocampus, and amygdala of their brains in order to follow changes in EEG as a result of treatment. After caffeine administration (0.970 mg/kg b.w., similar to what a person would get from a cup of tea or coffee), the researchers observed “a remarkably fast wave in the cortex and amygdala, and a rhythmical wave in the hippocampus … in the stimulant condition after caffeine administration compared with at rest.” Slow waves were also observed in the cortex and amygdala. The EEG changes indicated that 5 μmol/kg (0.970 mg/kg) b.w. (body weight) is the minimum dose of caffeine as a stimulant.

Ten minutes after i.v. administration of the caffeine, the rats were treated by i.v. with various doses (0, 5, 10, 25, and 50 μmol/kg (0.871, 1.742, 4.355, and 8.710 mg/kg) b.w. of theanine. Results showed that a suppressive effect of theanine on caffeine stimulation emerged at higher than 10 μmol/kg, (1.742 mg/kg) b.w. of theanine. At very low doses (2 μmol/kg (0.348 mg/kg) b.w.), however, theanine exerted a stimulatory effect.

This rat EEG study is consistent with the reports of theanine inducing feelings of relaxation and improved sleep quality5 and reduced physiological stress responses during a stressful task situation6 in human subjects that has appeared in recent research. Although theanine has been linked to improved sleep quality, it has also been reported to produce no drowsiness in humans.6B

Theanine Partially Counteracts Caffeine-induced Sleep Disturbance in Rats

In another recent (published this year) study of the effects of caffeine on sleep in rats,7 researchers found that 22.5 mg/kg and 37.5 mg/kg of theanine (but not 75 mg/kg or 150 mg/kg) significantly reversed the caffeine-induced decrease in SWS (slow wave sleep) but didn’t significantly affect the caffeine-induced increase in wakefulness or the decrease in REM sleep. This study used a much higher dose of caffeine than the Kakuda et al study4 discussed above (7.5 mg/kg intraperitoneally v. 0.97 mg/kg i.v.). Though none of the doses of theanine in this study reduced the time it took (latency) to sleep for an hour, the lowest dose of theanine produced a trend toward reduced latency that did not reach statistical significance, but came close (p=0.054).

A 2006 human study6 of the effects of theanine on stress involved 12 healthy volunteers (male undergraduate students, age range 20–25 years, mean = 21.50, S.D. (standard deviation), 1.38 years). The subjects performed a stressful mental arithmetic task and were assessed for changes in heart rate, heart rate variability, and salivary immunoglobulin A (s-IgA) as indicators of physiological stress. The researchers also determined the frequency domain of heart rate variability, which has a high frequency band (HF) and a low frequency one (LF). The HF band is said to be related to respiratory sinus arrhythmia and “is exclusively attributable to parasympathetic [cholinergic] influence reflecting vagal activity while the latter [LF] mirrors the baroreceptor feedback loop that controls blood pressure and appears to reflect both sympathetic and parasympathetic activity.”6 The LF/14F ratio was thought to reflect the sympathovagal balance. Our observation of the significant decrease in the HF component and a remarkably increased LF/HF ratio during the task indicated that the sympathetic nervous system was prominently activated by this [mental arithmetic] task.”6 In addition to these physiological changes, the subjects experienced acute feelings of stress and anxiety. With this background, the researchers felt this was a good experimental basis for evaluating the effects of theanine in a stressful situation.

The experimental subjects received 200 mg of theanine dissolved in 100 ml of water as treatment. To detect a possible time lag between when the theanine was administered and when it took effect, the authors gave the theanine to the subjects at two time points. The subjects performed the mental arithmetic for 20 minutes.

In previous studies, the researchers reported6 that they had found the mental arithmetic task to induce “remarkable” stress feeling and sympathetic (adrenergic) nervous activation reflected by elevated heart rate and s-IgA, an immunoglobulin, demonstrating a stress effect on the immune system,

The results were similar to expectations, although contrary to what the authors had thought, they didn’t find any significant differences between the theanine administered at the two time points. The post-hoc analysis indicated that the LF/HF ratio was significantly higher under the placebo condition than under theanine treatment, indicating that the participants had more activation of the sympathetic nervous system during the stress of the mental arithmetic under the placebo condition than when they had received theanine. The researchers stated in their discussion: “[t]he main findings in this study were that the acute stress responses elicited by the mental arithmetic task were reduced by the oral administration of L -theanine. Moreover, this effect of L -theanine was consistently observed not only in the subjective perception of stress but also in physiological stress responses such as HR [heart rate] and s-IgA. … after termination of the experimental sessions, no participants could identify whether they drank water or water containing L -theanine.” And, of course, the study was done double blind.

Because the researchers did not actually measure blood pressure, vascular resistance, noradrenaline, and adrenaline, they admit that they could only speculate about the changes in sympathetic nervous system activity on the basis of the HR, HRV, and s-IgA data. They suggest further studies of neural mechanisms and with a larger number of participants. They conclude by noting that despite the limitations of their study, the results suggest that L-theanine “was effective for reducing the stress responses elicited by the mental arithmetic task.”

Induction of Long Term Potentiation by Theanine in Young Rats

Researchers tested the effects of theanine treatment on long-term potentiation (LTP) induction at hippocampal CA1 synapses as well as the effects on acute stress in young rats receiving either water or water containing 0.3% theanine.8 Long term potentiation is a process that is an important part of learning.

EFFECT OF THEANINE ON STRESS HORMONES: Serum corticosterone level was markedly decreased six weeks after the start of theanine administration.

LONG TERM POTENTIATION: The researchers used electrical stimulation administered via implanted electrode to detect CA1 LTP in both theanine-treated rats and control rats. As they explained,8 “CA1 LTP consists of NMDA receptor-dependent and NMDA receptor-independent components.” “NMDA receptor-dependent and NMDA receptor-independent LTP mediate different aspects of acquisition and retention of spatial memory.” The influence of theanine on CA1 LTP under conditions of stress (tail suspension for 30 seconds) was examined. An hour after tail suspension, hippocampal slices were prepared for the experiment. The results showed that in the untreated (no theanine) control rats subject to tail suspension, CA1 LTP induced by a 100 Hz tetanus and by a 200 Hz tetanus was attenuated. But neither level of stimulation-induced CA1 LTP was attenuated in the theanine-administered rats. Hence. theanine intake modifies the mechanism of CA, LTP induction.”8

Effect of Theanine on Grain Monoamines and Striatal Dopamine Release in Rats

Another paper9 reports that theanine administered intragastrically at various doses resulted in significant increases in serotonin and/or dopamine concentrations in the brain, especially in the striatum, hypothalamus, and hippocampus. Direct administration of theanine via microinjection into the brain striatum resulted in dose-dependent increases in dopamine release. This dopamine release was significantly inhibited by pretreatment with an NMDA glutamate receptor antagonist. Another paper9B declared. [p]reclinical studies suggest that L-theanine increases a number of neurotransmitters including serotonin, dopamine and GABA, levels and has micromolar affinities for AMPA, kainate, and NMDA receptors,”

Theanine Increases Neurogenesis in Young Rats

Another paper10 reports facilitated neurogenesis in the developing hippocampus of young rats after the administration of 0.3% theanine in their drinking water. “Rearing behavior was significantly increased in theanine-administered rats, suggesting that exploratory activity is increased by theanine intake. Furthermore, object recognition memory was enhanced in theanine-administered rats.”10

Anti-Depressant-Like Effects of L-Theanine in the Forced Swim and Tail Suspension Tests in Mice

Another paper reports on anti-depressant-like effects in mice subject to the stressful forced swim and tail suspension tests. The mice pretreated with (or without) L-theanine at doses of 1, 4, and 20 mg/kg for 10 days were subject to the forced swim and tail suspension tests. The mice dosed with L-theanine had significantly reduced immobility time in response to these highly stressful tests as compared to the animals subject to the tests and receiving no theanine. “Taken together, these results indicate that L-theanine possessed an antidepressant-like effect in mice, which may be mediated by the central monoaminergic neurotransmitter system.”11

L-Theanine Improves Sleep Quality in Boys with Attention Deficit Hyperactivity Disorder

Does your workload sometimes pile up to where you feel as though you can hardly keep track of what you just did, let alone what you’re supposed to do next? If so, you have probably felt much like boys (or girls, though there are far fewer of them) who have ADHD (attention deficit hyperactivity disorder). This sense of overload can have a negative impact on your ability to sleep as well as to do productive work. A recent paper12 reported that L-theanine was safe and effective in improving sleep quality in 98 boys 8–12 years of age formally diagnosed with attention-deficit/hyperactivity disorder (ADHD).

The boys were treated with two chewable tablets (each containing 100 mg of L-theanine) twice daily (total 400 mg daily) or an identical tasting placebo. Those who received L-theanine experienced significantly higher sleep percentage and sleep efficiency scores, as indicated by the actigraph watches each subject wore—the watches are an activity-based sleep monitor that uses an accelerometer to detect wakefulness and patterns of sleep. Theanine did not, however, decrease the time it took subjects to fall asleep (latency) or sleep duration.


Most of your problems are probably due to how you respond to them—the stress that you experience—and that is something that you can do something about entirely independently of correcting the problems themselves. The hippocampus, a major center controlling cognitive processes, is enriched with glucocorticoid receptors and thus plays an important role in stress responses. Increasing stress can have negative effects on hippocampal-derived cognitive behavior and synaptic plasticity such as LTP (long term potentiation) involvement in memory.

Some new studies have indicated significant protection by L-theanine against stress. Examples include a paper13 reporting a protective effect by L-theanine in post-weaning mice subject to acute stress (such as being dunked in water), where the animals were treated with drinking water containing 0.3% L-theanine for 3 weeks before being stressed. Results showed decreased, levels of serum corticosterone (a stress hormone) in rats receiving L-theanine after water immersion stress. In addition, the treated rats did not have attenuation of LTP in their hippocampi unlike the control rats. The treated rats didn’t have a decreased object memory recognition following stress, as the control rats did.

Another example was a paper14 in which male mice were subject to psychosocial stress by being housed in a confrontational situation with other male mice. The ingestion of theanine (>5 μg/ml) prior to being put into the confrontational housing situation significantly suppressed the adrenal hypertrophy (increased size of the adrenal gland induced by stress).

And, a final example was a paper15 reporting on the protective effect of L-theanine against cognitive impairments and oxidative stress induced in mice put into a chronic restraint tube for 8 hours a day for 21 days. We would call being confined to a tube where you can barely move, even though the tube was well ventilated, and you were deprived of food and water a very severe stress. Yet, treatment with 4 mg/kg of L-theanine caused a statistically significant decrease in mistakes made in a test following the period of confinement stress; 2 mg/kg and up to 4 mg/kg of L-theanine only caused a tendency toward decreased mistakes that did not reach significance.

Finally, the L-theanine significantly inhibited the decrease in noradrenaline and dopamine levels induced by the chronic restraint stress in the hippocampus and cortex of the mice. These sorts of protective effects would be expected to produce a “normalizing” effect on the feelings and cognition of humans subject to severe stresses.

While we can’t say that being cooped up in a tube would be anything but unpleasant, you might come out of it with a much more positive mood by supplementing with L-theanine!


  1. Kakuda. Neuroprotective effects of the green tea components theanine and catechins. Biol Pharm Bull. 25(12):1513-8 (2002).
    2. Egashira et al. Involvement of GABAA receptors in the neuroprotective effect of theanine on focal cerebral ischemia in mice. J Pharmacol Sci. 105:211-4 (2007).
    3. Nishida et al. Altered levels of oxidation and phospholipase C isozyme expression in the brains of theanine-administered rats. Biol Pharm Bull. 31(5):857-60 (2008).
    3A. Egashira et al. Neuroprotective effect of gamma-glutamylethylamide (theanine) on cerebral infarction in mice. Neurosci Lett. 363;58-61 (2004).
    3B. Kobayashi et al. Effects of L-theanine on the release of alpha-brain waves in human volunteers. Nihon Nogeikakgaku Kaishi (in Japanese) 72:153-7 (1998) [we haven’t read this].
    4. Kakuda et al. Inhibiting effects of theanine on caffeine stimulation evaluated by EG in the rat. Biosci Biotechnol Biochem. 64(2):287-93 (2000).
    5. Ozeki, Juneja, and Shirakawa. The effects of theanine on sleep with physiological evaluation using actigraph. Proceedings of the 50th Meeting of Japan Society of Physiological Anthropology, Chiba (Oct, 25-26, 2003).
    6. Kimura et al. L-theanine reduces psychological and physiological stress responses. Biol Psychol. 74(1):39-45 (2006).
    6B. Itoh et al. Effects of L-theanine on the release of alpha-brain waves in human volunteers. Nippon Nogeikacaku Kaishi [in Japanese, so we have not read this] 72:153-7 (1996).
    7. Jang et al. L-theanine partially counteracts caffeine- induced sleep disturbances in rats. Pharmacol Biochem Behav. 101:217-21 (2012).
    8. Takeda et al. Unique induction of CA1 LTP components after intake of theanine, an amino acid in tea leaves and its effect on stress response. Cell Mol Neurobiol. 32:41-48 (2012).
    9. Yokogoshi et al. Effect of theanine, r-Glutamylethylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res. 23(5):667-73 (1998).
    9B. Nathan et al. The neuropharmacology of L-theanine (N-ethyl L-glutamine): a possible neuroprotective and cognitive enhancing agent. J Herb Pharmacother. 6(2):21-30 (2006).
    10. Takeda et al. Facilitated neurogenesis in the developing hippocampus after intake of theanine, an amino acid in tea leaves, and object recognition memory. Cell Mol Neuromol. 31(7);1079-88 (2011).
    11. Yin et al. Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice. Phytother Res. 25:1636-39 (2011).
    12. Lyon et al. The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind placebo-controlled clinical trial. Altern Med Rev. 16(4):348-54 (2011).
    13. Tamano et al. Preventive effect of theanine intake on stress-induced impairments of hippocampal long-term potentiation and recognition memory. Brain Res Bull. 95:1-6 (2013).
    14. Unno et al. Ingestion of theanine, an amino acid in tea, suppresses psycho­social stress in mice. Exp Physiol. 98(1);290-303 (2013).
    15. Tian et al. Protective effects of L-theanine on chTonic restraint stress-induced cognitive impairments in mice. Brain Res. 1503:24-32 (2012).
Information provided for educational purposes only. *These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.


Important Brain Nutrient
There is little published data specifically
on taurine’s effects on sleep.

By Durk Pearson & Sandy Shaw

Taurine is the second most abundant amino acid in the CNS (central nervous system), but also found ubiquitously in millimolar concentrations in all mammalian tissues.1 In cultured astrocytes, for example, intracellular taurine can be found at concentrations of 20 mM or more.2 Because of its widespread presence and high physiological concentration, taurine exerts a variety of effects throughout the body. For example, the effectiveness of taurine on diabetes mellitus alone include reducing insulin resistance and complications such as retinopathy, nephropathy, neuropathy, atherosclerosis and cardiomyopathy, and other antidiabetic effects independent of hypoglycemia, as reported in various animal models.1Moreover, taurine is a potent inhibitor of protein glycation and formation of AGEs (advanced glycation endproducts) that are responsible for many of the complications of diabetes as well as contributing importantly to other age-associated diseases.3

There is little published data specifically on taurine’s effects on sleep. Taurine has important effects on brain function. Yet, one would expect that due to taurine’s potent protective effects against excitotoxicity, for example, a variety of sleep dysfunctions stemming from excitotoxicity would be beneficially affected by taurine. We did not find much on taurine and sleep dysfunctions in the literature. However, there was a substantial amount of data on the neuroprotective effects of taurine in cell-damaging conditions (such as ischemia and hypoxia as well as excitotoxicity) in the developing and aging hippocampus.4 Saransaari and Oja report that under ischemic conditions, there is a massive release of taurine in the brain, which might be to deliver taurine to brain tissues as a defense against excitotoxicity. There are also data on the protective effects of taurine on cognitive function.5

Taurine has a wide margin of safety, being well tolerated at 2 grams/day or even (for most patients) up to 12 grams/day as an adjunct therapy for liver disease.6

Taurine May Be Neuroprotective Against Sleep Apnea

The brain release of taurine under ischemic conditions could be of considerable importance in individuals with sleep apnea, a common condition where individuals experience brief periods of no or little breathing during sleep (often accompanied by snoring), which transiently reduces tissue oxygen availability; excitotoxicity is induced during sleep apnea by glutamate in hippocampal neurons.7

Taurine is a neuromodulator, antioxidant, calcium ion regulator, and osmoregulator. Changes in taurine content in different brain areas with age vary depending upon the brain area and the conditions under which measurement takes place. For example, the taurine content of the striatum is decreased in old rats with learning deficits, but the decline was less severe in old rats that were not impaired in a spatial memory task.8 Excretion of taurine via the urine appears to be decreased with aging, suggesting that there is a need to conserve taurine and, as the authors of some papers have put it, reflects a condition of taurine deficiency with advanced aging.8–9

Taurine and Sleep Regulation

Interestingly, taurine has been reported to interact with neurotransmitter receptors involved in sleep regulation, including GABA-A, GABA-B, and glycine.2 As noted in Albrecht and Schousboe, 2005, “… in many instances taurine exerted its cytoprotective effects against excitotoxic and/or energy depriving insults in vitro by a mechanism involving interaction with GABA-A receptors. This is consistent with the fact that activation of GABA-A receptors counteracts the activation of NMDA receptors and generation of nitric oxide.” As of the time of the publication of this paper, however, the interaction of endogenous taurine with GABA-A receptors in vivo remained uncertain. The authors thus note, “[b]y far the strongest evidence speaks in favor of glycine receptors being the major and most specific target of endogenous taurine.” However, they also noted that, “exogenous taurine has in many instances turned out to have profound neuroprotective effects, many of which can be ascribed to interaction with GABA-A receptors.” Sometimes it seems that the more you know, the more complex biological systems seem to become!

Taurine Protection Against the Neurotoxicity of Beta Amyloid and Glutamate Receptor Agonists in Alzheimer’s Disease

Accumulation of beta amyloid is a well-known factor in the development and progression of Alzheimer’s disease which has been linked to other neurodegenerative disorders as well via overactivation of glutamatergic neurotransmission and excitotoxicity. In a fairly recent paper, the researchers reported that taurine protected chick retinal neurons in culture against the neurotoxicity of amyloid beta and glutamate receptor agonists. The authors suggest that taurine might also provide protection against other neurodegenerative diseases such as Huntington’s disease, amyotrophic lateral sclerosis, AIDS dementia complex, and Parkinson’s disease, as well as acute insults leading to massive brain cell death as a result of excitotoxicity such as hypoglycemia, neurologic trauma, stroke, and epilepsy. The authors claim that their study showed for the first time that taurine prevents the neurotoxicity of beta amyloid and that that protection is related to the activation of GABA-A receptors. As they also report, other GABA-A agonists, including melatonin, carbamazepine, phenyloin, and valproic acid have also been shown to attenuate the neurotoxic effects of beta amyloid, the latter three by stabilization of intracellular calcium levels.6

Taurine as a Scavenger of Reactive Carbonyl Species and Inhibitor of Protein Glycation and AGE Products

In the presence of high concentrations of glucose or fructose, proteins are at high risk of glycation (the chemical interaction between certain sugars and proteins) resulting in the formation of AGEs (advanced glycation endproducts), which have been found to be important causative factors in the development and progression of many age-associated diseases including diabetes, atherosclerosis, osteoarthritis, and cataract.3,10–11

Taurine is one of a few important endogenous low molecular weight chemicals (including, in addition to taurine, carnosine, histamine, and pyridoxamine, the latter being a form of thiamine that was until recently available as a dietary supplement but has now been declared a prescription drug by the FDA) that provide protection against reactive carbonyl species (intermediates of oxidative stress and glycation) and AGEs. In a fairly recent study,3 researchers found that taurine prevented in vitro glycation and the accumulation of AGEs and, in in vivo studies with rats, the contents of glucose, glycated protein, glycosylated haemoglobin and fructosamine were significantly lowered by taurine treatment in high fructose diet-fed rats.

Probably because of its wide variety of functions, it is difficult to pin down the exact mechanism of taurine in each of its protective effects. For example, it is not known how much of the excitotoxic damage that occurs in the brain induces taurine release to ameliorate some of that damage. Yet, because taurine is found in such high quantities in the brain, it is reasonable to assume that its release may be neuroprotective during episodes of excitotoxicity. All the more reason that additional research should be done to identify in more detail how this important molecule works.

Taurine Improves Learning and Memory Retention in Aged Mice

Yet another major benefit provided by taurine was reported in a 2008 paper,12 where chronic supplementation with taurine in aged mice significantly ameliorated the age-dependent decline in memory acquisition and retention. “These changes include increased levels of the neurotransmitters GABA and glutamate, increased expression of glutamic acid decarboxylase and the neuropeptide somatostatin and increase in the number of somatostatin-positive neurons. These specific alterations of the inhibitory system caused by taurine treatment oppose those naturally occurring in aging, and suggest a protective role of taurine against the normal aging process.”12 The author states (with references provided) that taurine has been shown to act as an agonist of GABA-A receptors. As we noted above, GABA-A is involved in sleep.

Cholinergic Dysfunction as a Result of Excitatory Amino Acids May Be Responsible for Cognitive Decline

Another possible mechanism that may contribute to cognitive dysfunction is the inhibition of choline acetyltransferase reported to take place as a result of the action of excitatory amino acids in the central nervous system.13 Although this paper did not test for the protective effects of taurine against these deleterious effects of excitatory amino acids, it is reasonable to suppose that taurine, found in high concentrations in the brain and known to have protective effects against excitotoxicity, would provide some protection. We hope that researchers will follow up on this. Choline acetyltransferase is the enzyme responsible for converting choline to acetylcholine; hence, its activity is critical for normal cholinergic function in the CNS.

In the choline acetyltransferase paper, researchers studied the effects of excitotoxic amino acids on retinas from 8–9 day old chick embryos. Exposure to 15 hours of treatment with kainate or glutamate resulted in maximal inhibition (80–90%) of choline acetyltransferase. The data suggested that the effect of excitatory amino acids was caused by a reduction in the enzyme activity rather than a reduction in the cellular content of the enzyme.

Glutamate Receptor-mediated Taurine Release During Oxidative Stress in the Hippocampus

Excitotoxicity as a result of oxidative stress induced by glutamate in the hippocampus was reported in another paper to cause taurine release. The authors here concluded that: “Taurine efflux via VRAC [volume-regulated anion channel] is critical for volume regulation of hippocampal slices exposed to oxidative stress. This increased taurine efflux does not result from direct activation of the taurine release pathway by H2O2 [hydrogen peroxide]. NMDA receptor activation plays an important role in taurine release during oxidative stress.” The authors explain that “[r]eactive oxygen species may directly precipitate brain swelling without inducing ischemia or blood-brain barrier injury during intracranial hemorrhage and excitotoxic injury.”14

Mental Fatigue

In another paper, the authors hypothesized that mental fatigue, a type of mild neurocognitive disorder, may be associated with impaired clearance of glutamate from extracellular space to prevent excitotoxicity. Mental fatigue is prominent after sleep deprivation and patients with the disorder are reported to suffer from sensitivity to loud sounds and light, irritability, affect lability, stress intolerance, and headaches. Factors that the authors identify that can impair astroglial glutamate transport are arachidonic acid, lactic acid, cytokines, and leukotrines, nitric oxide, beta amyloid protein, peroxynitrite, and gluco­corticoids.15

Considering the potential relationship between “mental fatigue” and excitotoxicity in relation to stress, we would be interested in a specific study of the possible protective effects of taurine against “mental fatigue.”

Personal Note on Formulation Development

Since we developed this formulation for our own use, we used the scientific literature to locate appropriate papers, which we read and then used to select candidate ingredients. We then tried various combinations of these ingredients and found—subjectively—that each makes a difference, including taurine.


  1. Ito et al. The potential usefulness of taurine on diabetes mellitus and its complications. Amino Acids. 42:1529-39 (2012).
  2. Albrecht and Schousboe. Taurine interaction with neurotransmitter receptors in the CNS: an update. Neurochem Res. 30(12):1615-21 (2005).
  3. Nandhini et al. Stimulation of glucose utilization and inhibition of protein glycation and AGE products by taurine. Acta Physiol Scand. 181:297-303 (2004).
  4. Saransaari and Oja. Enhanced taurine release in cell-damaging conditions in the developing and ageing mouse hippocampus. 79(3):847-54 (1997).
  5. Dawson et al. An age-related decline in striatal taurine is correlated with a loss of dopaminergic markers. Brain Res Bull. 48(3):319-24 (1999).
  6. Louzada et al. Taurine prevents the neurotoxicity of beta-amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer’s disease and other neurological disorders. FASEB J. 18:511-8 (2004).
  7. Fung et al. Apnea promotes glutamate-induced excitotoxicity in hippocampal neurons. Brain Res. 1179:42-50 (2007).
  8. Dawson. Taurine in aging and models of neurodegeneration. in Taurine 5: Beginning the 21st Century (edited by Lombardini, Schaffer, and Azuma, Kluwer Academic/Plenum Publishers (2003).
  9. Corman, et al, 1985
  10. Nandhini and Anuradha. Inhibition of lipid peroxidation, protein glycation and elevation of membrane ion pump activity by taurine in RBC exposed to high glucose. Clin Chim Acta. 336(1-2):129-35 (2003).
  11. Li et al. Direct reaction of taurine with malondialdehyde: evidence for taurine as a scavenger of reactive carbonyl species. Redox Rep. 15(6):268-74 (2010).
  12. El Idrissi. Taurine improves learning and retention in aged mice. Neurosci Lett. 436:19-22 (2008).
  13. Loureiro-Dos-Santos et al. Inhibition of choline acetyltransferase by excitatory amino acids as a possible mechanism for cholinergic dysfunction in the central nervous system. J Neurochem. 77(4):1136-44 (2001).
  14. Tucker and Olson. Glutamate receptor-mediated taurine release from the hippocampus during oxidative stress. J Biomed Sci. 17 (Suppl 1):S10 (2010).
  15. Ronnback and Hansson. On the potential role of glutamate transport in mental fatigue. J
Information provided for educational purposes only. *These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.

Choline in Brain Function and Sleep

Choline in Brain Function and Sleep 
Acetylcholine (made from choline) is an important part of regulatory pathways in sleep and many cognitive functions.

By Durk Pearson & Sandy Shaw

Areview in Neuron1 described the function of acetylcholine (a ubiquitous neurotransmitter) in the brain as follows: “Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity, and coordinates firing of groups of neurons.” Its many effects make acetylcholine “an essential mechanism underlying complex behaviors.”1 Further, they propose a common theme for the activities of acetylcholine: “that acetylcholine potentiates behaviors that are adaptive to environmental stimuli and decreases responses to ongoing stimuli that do not require immediate action.”

The complex interaction between the cholinergic nervous system and the dopaminergic system includes regulation by cholinergic interneurons through muscarinic cholinergic receptor signaling as critical components in striatum-dependent decision making, which also involves dopaminergic signaling for the detection of rewarding stimuli.2 Cholinergic interneurons “can regulate the duration, magnitude, and spatial pattern of activity of striatal neurons, potentially creating an attentional gate that facilitates movement toward salient stimuli.”1 Moreover, as noted in the review,1 “the function of striatal cholinergic interneurons is also impaired in patients with movement disorders involv[ing] the dopaminergic system, such as Parkinson’s and Huntington’s disease …”


  1. Picciotto et al. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 76:116-28 (2012).
    2. Mark et al. Cholinergic modulation of mesolimbic dopamine function and reward. Physiol Behav. 104:76-81 (2011).

Circadian Rhythm of the Cholinergic Nervous System

As described in another paper,7 “[t]here is [] a pronounced circadian rhythm in the activity of the cholinergic system, upon which sleep, waking, and fundamental aspects of learning depend. These rhythms may deteriorate with aging, and sleep disturbance is a particular problem in AD [Alzheimer’s disease].” The authors focused upon the differences between the effects of administering cholinergic agonists during specific times of day. As they explain, “[t]he cholinergic system is regulated for increased transmission during waking and motor activity and decreased transmission (in general, during sleep, with brief, localized increases during rapid eye movement (REM) sleep. The elements of the cholinergic system—synaptic acetylcholine (ACh), stored ACh, acetylcholinesterase (AChE) activity and cholinergic receptors—are coordinated to achieve this end.” The experiments were done using cats.

In the cortex of the cats, ACh was reported to be doubled during quiet waking and nearly tripled when cats were activated by listening to tapes of singing birds. By contrast, during REM sleep, ACh was doubled in the cortex and tripled in the hippocampus. Thus, as has been reported elsewhere, ACh release is increased during waking, motor activity, and REM sleep.

As also reported in paper #7, cholinergic stimulation during the night in humans has effects similar to that seen in the animal studies. Cholinergic stimulation during NREM (non-REM) sleep induces awakenings and decreases in sleep time and efficiency, while cholinergic activity can enhance REM sleep. The authors describe studies that suggest that cholinergic inactivity during non-REM sleep may be a critical link in the consolidation of declarative memory (that includes word lists and places). Specific studies on galantamine (described in detail) did not find significant changes in the Pittsburgh Sleep Quality Index, did not find increased insomnia/sleep problems as compared to patients on placebo, but there was a suggestion of increased REM sleep activity (nightmares) at 24 mg/day. The authors7 note that the key to avoid unwanted cholinergic effects on sleep with cholinesterase inhibitors is to note their half-life (about 7 hours with galantamine)—indicating the period of increase and decrease of cholinergic activity—so as not to be increasing cholinergic activity excessively during sleep. With a 7 hour half-life, twice daily administration of immediate-release galantamine with meals, thus covers the normal waking day (data on file, Janssen Pharmaceutica Products LP, 2004) Low-dose choline taken by late afternoon should not have these effects.

  1. Davis and Sadik. Circadian cholinergic rhythms: implications for cholinesterase inhibitor therapy. Dement Geriatr Cogn Disord. 21:120-9 (2006).

Cholinergic Mechanisms for REM Sleep Control

“Rapid eye movement (REM) sleep is a distinct high frequency oscillation arousal state that has been linked to several aspects of brain function including developmental maturation of the brain, modification of synaptic plasticity and memory formation, as well as regulation of metabolic functions.”6 “Of particular importance are clusters of putative cholinergic neurons within the pedunculopontine (PPN) and laterodorsal tegmental (LDT) nuclei that have been characterized as ‘REM-on’ neurons because of increased firing during REM sleep. The combined data obtained from in vivo, lesion, transection, and pharmacological studies have suggested that these putative cholinergic ‘REM-on’ neurons in the brainstem are critically important for the generation and maintenance of the REM sleep state via widespread projections to the thalamus, brainstem, and specifically to the anterior pons.”6

The authors of paper #6 explain that various lesion and anatomical studies have suggested that the dorsal subcoeruleus (SubCD) area of the brain plays a major role in the production of REM sleep atonia (muscle paralysis) via descending projections to the medulla and spinal cord. The researchers performed experiments on SubCD brain slices to study the effects of the cholinergic agonist carbachol on SubCD brain activity, finding that carbachol “exerts a predominantly inhibitory role on fast synaptic glutamatergic activity and a predominantly excitatory role on fast synaptic GABAergic/glycinergic activity in the SubCD.” They conclude by hypothesizing that during REM sleep, cholinergic “REM-on” neurons that project to the SubCD induce an “excitation of inhibitory interneurons and inhibition of excitatory events leading to the production of coordinated activity in the SubCD projection neurons,” in which this coordination may be essential for the production of REM sleep.

This provides a sample of the complexity of sleep research at the molecular level and the contribution of the cholinergic nervous system to REM sleep. The authors remind readers that brain slices do not have sleep-wake cycles and, therefore, this is a limitation of the study. The work thus reveals the details of biochemical interactions in the SubCD at the molecular level but these do not provide the wider picture available with the addition of sleep-wake cycles that also involve other areas of the brain.

  1. Heister et al. Cholinergic modulation of GABAergic and glutamatergic transmission in the dorsal subcoeruleus: mechanisms for REM sleep control. Sleep. 32(9):1135-47 (2009).

The Cholinergic Nervous System as a Major Regulator of Inflammation

The parasympathetic nervous system is regulated by acetylcholine and plays a major role in modulating inflammation induced by the immune system in response to pathogens and inflammatory cytokines released in the process of tissue repair. In a severe form of runaway inflammation, sepsis resulting from infection has a high mortality rate. The vagus nerve, carrying cholinergic signals, is an important part of the parasympathetic nervous system anti-inflammatory activity via the conveyance of information to and from the brain. For example, in a model of endotoxemia (bacterial infection releasing endotoxins that stimulate release of inflammatory cytokines), “electrical stimulation of the vagus nerve significantly reduced serum and liver TNF [tumor necrosis factor, a major inflammatory cytokine] levels, prevented development of haemodynamic shock and improved survival without significantly altering IL-10 [an antiinflammatory cytokine] or corticosterone serum levels.”3

As reported in paper #3, “[s]uppression of inflammation in the brain and in the periphery can be achieved by enhancing cholinergic signaling by administration of acetylcholinesterase inhibitors. The acetylcholinesterase inhibitor galantamine, acting through a central mechanism, has been shown to attenuate serum TNF and IL-6 and improve survival in a murine [mouse] model of endotoxaemia.” Choline, as the precursor to the production in the body and brain of acetylcholine, is also able to enhance cholinergic signaling. “This mechanism could explain the association between high choline dietary intake with reduced pro-inflammatory markers in serum.”3

In fact, an editorial in a 2008 issue of the American Journal Of Clinical Nutrition4 commented on the finding of a paper in that issue that higher dietary intakes of choline and betaine decreased biomarkers of inflammation and was of the same magnitude as those reported for the Mediterranean Diet as a whole. (This was an epidemiological study; thus, this was an association that didn’t by itself prove causality.) Still, the author titled his editorial, “Is there a new component of the Mediterranean diet that reduces inflammation?”

  1. Rosas-Balina and Tracey. Cholinergic control of inflammation. J Intern Med. 265:663-79 (2009).
    4. Zeisel. Is there a new component of the Mediterranean diet that reduces inflammation? Am J Clin Nutr. 87:277-8 (2008).
Information provided for educational purposes only. *These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.

GLYCINE By Durk Pearson & Sandy Shaw®

GLYCINE By Durk Pearson & Sandy Shaw®

Glycine is a semi-essential amino acid. It is semi-essential because, although it is made in the body, it may not be produced in quantities that are adequate for all the uses of glycine under all conditions.A The authorsA did a detailed assessment of all possible sources of glycine and all its metabolic uses, including collagen synthesis (collagen being the most abundant protein in the human body) and concluded that “glycine is a semi-essential amino acid and [] it should be taken as a nutritional supplement to guarantee a healthy metabolism.” They do note that a deficiency of glycine is not life-threatening, even in the worst of cases, but that a chronic shortage may result in detrimental effects on the quality of life, such as a slower turnover of collagen (which also occurs as a result of aging), which would increase the likelihood of collagen becoming modified (such as increased cross-linking that decreases plasticity). It is also interesting to noteA that Directive 67/548/EEC of the European Union describes glycine as “not hazardous,” as it does not become toxic in rats when taken orally until a gigantic dose of 8 g/kg is reached, corresponding to around 600 g in a human.”

Glycine Improves Sleep Quality

A 2012 paper1 describes glycine as a non-essential amino acid* that has indispensable roles in both excitatory and inhibitory neurotransmission via NMDA (N-methyl-D-aspartate) type glutamate receptors and glycine receptors, respectively. The authors of this paper1 report the results of their trial of the effects of glycine supplementation on the sleep quality of rats and of humans complaining of insomnia problems.

* As we explain at the beginning of this article, glycine is probably “semi-essential” rather than non-essential. In paper #1, however, the authors have described it as non-essential. “Non-essential” doesn’t mean that it doesn’t have an important physiological function, but that, under usual conditions, you don’t have to get much of it from your diet because you are able to manufacture most of what you need within your own body. One source of information1 states that, in humans, approximately 45 g of endogenous glycine is synthesized by the body per day, while 3–5 g is taken up from the diet in a day.

Consistent with the reduced core body temperature that occurs in conjunction with the onset of sleep, glycine supplements in rats were accompanied by a reduction in core body temperature associated with an increase in skin blood flow. In addition, glycine was found to passively diffuse across the blood brain barrier by nonspecific transport. The cortical levels of glycine reached a level 2-fold higher than that attained by the animals received only vehicle. A dose of 2 g/kg of glycine increased plasma glycine concentration to a level 13 fold higher than that of control animals given vehicle alone at 30 minutes

 Did the Rats Have a Good Night’s Sleep?

Well, we don’t know for sure since the rats didn’t say, but the data suggests they did. The data in a previous study by these same authors indicated that oral administration of glycine increased extracellular serotonin release in the rat prefrontal cortex, which would be expected to enhance the sleep process. In the extant study,1 the effect of glycine on sleep in the rats was assessed by EEG/EMG recordings. “Glycine (2 g/kg) significantly increased non-REM (NREM) sleep and reduced wake state in sleep-disturbed rats after 2 h of oral administration. When glycine was bilaterally injected into the SCN (suprachiasmatic nucleus, the center for regulating circadian rhythms), it acted on NDDA receptors in the SCN, resulting in vasodilation (as indicated by increased cutaneous blood flow) and decreased core body temperature. Hence, the sleep-inducing pathway was enhanced in the rats.

The Effects of Glycine on Sleep in Humans

The researchers also investigated the effects of glycine on sleep quality in people with sleep complaints. These subjects were given 3 grams of glycine or a placebo just before bedtime. The study (a randomized double-blind crossover study) included 19 female volunteers 24–53 years of age, average 31.1). Their sleep quality was assessed by a standard measure, the Pittsburgh Sleep Quality Index. At scores of 6 or greater, this was said to indicate that the subjects had continuously experienced unsatisfactory sleep. The subjects were also evaluated for their subjective quality of sleep following the glycine (or placebo) treatment using the St. Mary’s Hospital (SMH) Sleep Questionnaire and the Space Aeromedicine (SAM) Fatigue Checklist. Glycine was found to significantly reduce the feeling of fatigue the next morning, supporting an improvement in sleep quality by glycine.

Glycine was found to significantly reduce the feeling of fatigue the next morning,
supporting an improvement in sleep quality by glycine.

The researchers had also published an earlier study of the improvement by glycine (3 grams just before bedtime) of sleep quality in a randomized, single blinded study of human volunteers.2 In that study, subjects (11 healthy volunteers, 8 female, 3 male) had improved subjective sleep quality, lessened daytime sleepiness, and improved performance of memory recognition tasks. In the paper published the year before3 by the same authors, 19 female volunteers complaining about poor sleep were subjects in a similar glycine trial (3 grams just before bedtime) that was a randomized, double blinded, cross-over type. The glycine ingestion was reported to significantly improve “fatigue,” “liveliness and peppiness,” and “clear-headedness.”

Possible Mechanisms for Glycine’s Effects on Sleep

Because the sleep studies reported above were all done by the same group or mostly the same group of researchers, it is particularly important to identify plausible mechanisms for an effect of glycine on sleep. We found such data and describe them here.

The glycine ingestion was reported to significantly improve “fatigue,” “liveliness and peppiness,” and “clear-headedness.”

Evidence That Glycine Mediates the Inhibition of Muscular Activity During Active Sleep

A 1989 paper4 describes researchers’ findings that there is a non-REM period during active sleep in which muscular movement controlled by spinal cord motoneurons is inhibited (atonia) principally by glycine or a glycinergic substance. (The cholinergic nervous system is involved in atonia during REM sleep.) This study used 5 normally respiring intact cats as subjects. The administration of strychnine (an antagonist of glycine) to the motoneurons of the cats prevented the atonia. Antagonists of GABA, the other major inhibitory neurotransmitter did not affect the muscular atonia of sleep.

Glycine is an inhibitory neurotransmitter. What happens if glycine neurotransmission is blocked? The excitatory poison strychnine blocks the glycine receptors, causing abnormal neurological excitation in the brain and, at higher doses, death by convulsions.

Glycine Increases Extracellular Serotonin But Not Dopamine in the Prefrontal Cortex of Rats

Researchers who were studying the beneficial effects of glycine in reducing negative symptoms of schizophrenia became interested in glycine because of its improvement of sleep quality.1 Exploring possible mechanisms to explain glycine’s effects on sleep, they discovered5 that oral administration of glycine in rats significantly increased extracellular serotonin levels in the rat prefrontal cortex for 10 minutes in the animals receiving 1 g/kg glycine, whereas there was no change in dopamine levels. (D-Serine, another amino acid tested in this model, also increased extracellular serotonin, although L-serine did not. D-Serine is the unnatural form of serine and is not present in one’s diet or one’s body.) The animals receiving 2 g/kg of glycine had serotonin levels significantly higher for 20–30 minutes after administration. For D-serine, post hoc analysis showed a significant increase of serotonin at 0–10, 60–70, and 100–110 minutes after administration. As before, L-serine did not induce significant changes. The authors hypothesize that “the effects of glycine on sleep disorders and negative symptoms of schizophrenia may be associated with an increase of serotonin in the PFC [prefrontal cortex].”

We believe that glycine is a preferred means for obtaining a short-term
serotonin increase, such as would be appropriate for a nap.

The researchers note that the increase in serotonin they observed was very short compared to that of a selective serotonin reuptake inhibitor, such as citalopram or venlafaxine, which they say increase brain serotonin for more than 180 minutes in the rat frontal cortex. They suggest that further research is needed to clarify the results they found. We believe that glycine is a preferred means for obtaining a short-term serotonin increase, such as would be appropriate for a nap.

“Glycine may potentially be useful in the treatment or prevention of lung inflammation due to inhaled particles.”

The Interaction Between Glycinergic Neurons and Orexin Neurons

A different group of researchers6 studying the effects of glycine in sleep reported that glycine had a direct effect on orexin neurons in cell culture, causing the latter to cease firing. This was interesting to the authors because orexin neurons are involved in the regulation of sleep; disruption of orexin signaling is the cause of narcolepsy, in which people can fall asleep without warning at any time. As a result of the experiments done as part of this study,6 the authors concluded that their observations indicated that the glycine receptor is expressed in glycinergic synapses in orexin neurons. “We recently found that specific pharmacogenetic inhibition of orexin neurons during the active period decreased wakefulness time and increased NREM sleep time in the dark period.” “For example, extracellular serotonin levels are reported to be increased after oral administration of glycine. Since we found serotonin directly inhibits orexin neurons, glycine administration might partly inhibit orexin neurons through serotonin.”6

Poor respiration is a common cause of sleep problems.

The researchers suggest further research to reveal additional details of the complex regulation of sleep.

Glycine Blunts Increases in Inflammatory Cytokines in Alveolar Macrophages

“Because alveolar macrophages are critically involved in the pathogenesis of many pulmonary diseases caused by inhaled particles and endotoxins [such as lipopolysaccharides, LPS, released by bacteria], [ ] studies were designed to test the hypothesis that alveolar macrophages could be inactivated by glycine via a glycine-gated chloride channel.”7 The authors7 explained that the inhalation of organic or cotton dusts, which they report to be highly contaminated with bacterial endotoxin (LPS), result in the overproduction and release of free radicals (such as superoxide) and the inflammatory cytokine TNF-alpha largely from alveolar macrophages as a result of increases in [Ca2+]. Their study7 reported that glycine at 100 μM or more blocked the increased [Ca2+] and LPS-induced production of superoxide in alveolar macrophages. Moreover, the authors explain, the superoxide from macrophages “is largely generated from molecular O2 through NADPH oxidase, an enzyme complex activated by phosphorylation by calcium-dependent protein kinases. By blunting the increase in [Ca2+] with glycine, the production of superoxide is reduced most likely by inhibiting calcium-dependent signaling required to activate NADPH oxidase.” The authors suggest that “glycine may potentially be useful in the treatment or prevention of lung inflammation due to inhaled particles.” In a different paper,8 glycine was reported to protect against endotoxin shock (sepsis) in the rat by inhibiting TNF-alpha (tumor necrosis factor alpha) production and increasing expression of IL-10, an anti-inflammatory cytokine. Poor respiration is a common cause of sleep problems.


  1. Melendez-Hevia et al. A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. J Biosci. 34(6):853-872 (2009).
    1. Bannai and Kawai. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J Pharmacol Sci. 118:145-148 (2012).
    2. Yamadera et al. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep Biol Rhythms. 5:126-131 (2007).
    3. Inagawa et al. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep Biol Rhythms. 4:75-77 (2006).
    4. Chase et al. Evidence that glycine mediates the postsynaptic potentials that inhibit lumbar motoneurons during the atonia of active sleep. J Neurosci. 9(3):743-51 (1989).
    5. Bannai et al. Oral administration of glycine increases extracellular serotonin but not dopamine in the prefrontal cortex of rats. Psychiatry Clin Neurosci. 65:142-9 (2011).
    6. Hondo et al. Orexin neurons receive glycinergic innervations. PLoS ONE. 6(9):e25076 (Sept. 2011).
    7. Wheeler and Thurman. Production of superoxide and TNF-alpha from alveolar macrophages is blunted by glycine. Am J Physiol. 277 (5 Pt 1):L952-9 (1999).
    8. Spittler et al. Immunomodulatory effects of glycine on LPS-treated monocytes: reduced TNF-alpha production and accelerated IL-10 expression. FASEB J. 13:563-571 (1999).
Information provided for educational purposes only. *These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease.
*The products and statements made about specific products on this web site have not been evaluated by the United States Food and Drug Administration (FDA) and are not intended to diagnose, treat, cure or prevent disease. All information provided on this web site or any information contained on or in any product label or packaging is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional. You should not use the information on this web site for diagnosis or treatment of any health problem. Always consult with a healthcare professional before starting any new vitamins, supplements, diet, or exercise program, before taking any medication, or if you have or suspect you might have a health problem.


The Sleeping Brain Decides What to Remember and What to Forget


Durk Pearson & Sandy Shaw’s Life Extension News Volume 16 No. 4 – April 2013

A new paper1 describes the sleep-dependent memory-processing factory that decides what to do with all that information you encountered during the day. As the paper’s authors point out, only some of that information is consolidated so as to become a part of a long-term knowledge base. The paper sifts through evidence from studies of naps, sleep deprivation, correlations of sleep stages and memory processing, sleep physiology, regional brain activity measured during and after sleep with PET and fMRI studies, cellular firing patterns, and synaptic and intracellular measures of plasticity to conclude that there is convincing evidence of sleep processing of memory with improvement of the overall knowledge base.

The authors discuss the new understanding that not all information is uniformly preserved, but that there is an exquisite selection process of memories underway during sleep. For example, they report that emotional memories can be selectively consolidated, especially during rapid eye-movement (REM) sleep. It has also been found that memories can be selectively maintained when they contain information on potential monetary rewards. Interestingly, when subjects of sleep memory studies have been told that they would be tested on certain areas of information and not on others provided before sleep, they were found after sleep to have retained more of the information they were told they would be tested on. Hence, the brain “knew” what to do to recall the relevant information.

Moreover, the authors explain, it is possible for the brain to generate new information during the processing of the memory-derived information. “Whether consolidation necessarily precedes these integrative processes (serial processing) is not yet known, but no clear cases of integration without consolidation have been observed. We use the term ‘memory evolution’ to reflect both the qualitative changes that can occur during such integrative processing and the extended time course over which they occur.”1 In gist extraction, the authors refer to the identification of commonalities between items in a collection of memories even when individual item memories are forgotten. Some studies have been found to show that during sleep subjects can extract overarching rules that govern recently studied sets of information, such that understanding of relationships between the sets is improved following sleep.

One study reported by the authors dealt with subjects taught a rote method for solving a class of mathematical problems for which there was a shortcut solution (about which subjects were not told). After a night of post-training sleep, however, subjects were found to be 2.6 times more likely to discover this shortcut than after an equal period of time awake (59.1 versus 22.7% of subjects).1 But, interestingly, even those who did not discover the shortcut benefitted from sleep by improving the speed with which they were able to perform the rote method of solving the problems. Those who became faster without discovering the shortcut improved their speed (using the rote method) three times more than either those who discovered the shortcut or those who remained awake.

This study examines important sleep processes at a systems level rather than at a neurotransmitter level. Understanding sleep involves comprehending its mechanisms from the micro-level details (neuro­transmitters and synapses) to the overarching system architecture.


  1. Stickgold and Walker. Sleep-dependent memory triage: evolving generalization through selective processing. Nat Neurosci. 16(2):139-45 (2013).

The ‘Will to Win’ Starts (with the neurotransmitters) in your Head

pryor-grounderThey say in professional sports, and with athletics at many levels, that the game is 90 percent mental and 10 percent physical.
As a professional baseball player from 1971 to 1987, I trained very hard and tried to eat healthy foods to get an edge. During my 16-year career I played in the major leagues for the Texas Rangers, Chicago White Sox and Kansas City Royals. A MLB player must have physical and mental strength to make split-second decisions. Because of the pressure to perform, many pro athletes try to get an edge through legal and illegal substances.
It was not until 1991 (after I retired from baseball) that I discovered that the brain (that mental side of the 90:10 equation),
can operate more effectively if you provide it with the right amount of nutrients in the right combinations.
In your brain are ten billion neurons (brain cells). Between each and every neuron are neurotransmitters. Everything that happens in the brain…every memory… every thought…every emotion…every innovation…every “wow, that’s great!”… is a result of the release of neurotransmitters.
Neurotransmitters are natural substances made by nerve cells in your brain that transmit messages from one nerve cell to another. Our bodies make them from food we consume or get the ingredients to make them from or dietary supplements.
It is estimated 86 percent of Americans have less than optimal levels of neurotransmitters. That’s why many have brain fade because our brains aren’t making enough neurotransmitters.
The three most important neurotransmitters that support brain function and can help athletes or those of us in everyday life are noradrenaline, dopamine, and acetylcholine.
There are two kinds of neurotransmitters inhibitory and excitatory. Excitatory neurotransmitters stimulate the brain. Inhibitory neurotransmitters calm and balance the brain. Inhibitory neurotransmitters can easily be depleted when excitatory neurotransmitters are overactive.
NORADRENALINE (norepinephrine)
Noradrenaline is an excitatory neurotransmitter and is nature’s “natural speed.” It is your “get up and go” juice. If you have enough of it you’re full of energy, you’re excited, and you’re self confident. This is what you want working for you when you compete in sports or head off to work in the morning.
Low noradrenaline levels are associated with low energy and decreased focus. Noradrenaline is created through an essential amino acid called phenylalanine. Essential amino acids can’t be created by your body. You can only get them from food or dietary supplements. With the help of certain nutrients such as vitamin B6, vitamin C, folic acid and copper, phenylalanine is converted into two neurotransmitters noradrenaline and dopamine.
By combining a little bit of caffeine with the nutrients listed above, you will (if you are like most people) experience long-lasting energy that really keeps you going, You can work longer and more productively and still have some energy left to enjoy your evening or weekend. But note, caffeine by itself does not help you make more noradrenaline. So while that morning cup of coffee (or caffeinated beverage) can give you a quick surge of energy and ambition, it doesn’t last very long and each succeeding cup does less for you than the prior one.
Dopamine is a special neurotransmitter because it is considered to be both excitatory and inhibitory. When dopamine is low we can have focus issues such as not remembering where we put our keys, forgetting what a paragraph said when we just read it or simply daydreaming and not being able to stay on task. Dopamine is also responsible for our drive or desire to get things done – our motivation. Dopamine is made from phenylalanine, so when you take phenylalanine, plus other nutrient cofactors, you’re able to make more dopamine.
Acetylcholine is the neurotransmitter that helps you with memory and organization – the way you order things in your mind, the way you retrieve them in an orderly manner. It’s also involved in focus and concentration. Your body manufactures acetylcholine from the essential nutrients choline and vitamin B5. The vitamin B5 (also known as pantothenate) acts to convert the choline to acetylcholine more efficiently.
Side Note: Prior to entering a game during my baseball career, I would occasionally smoke a cigarette (that I would steal from a teammate). My concentration seemed to be enhanced and the game seemed to “slow down.” It was not until I was retired that
I found out that nicotine causes the release of acetylcholine in the brain.
As you age, the ability to transport choline from your bloodstream into your brain drops dramatically. By the time most people hit their 60s they have only 20-30 percent of this ability that they had when they were young adults. That’s why people sometimes have “Senior Moments.” Studies at MIT have shown a correlation between the decrease in production of acetylcholine and Alzheimer’s disease. Increasing acetylcholine in the brain improves memory.
In these times, competition in sports and in business is at an all-time high. The ability to think more clearly and effectively and the drive to succeed are all tied directly to your brain’s ability to create adequate neurotransmitters.
If you provide your body (and brain) with the proper nutrients to make neurotransmitters, it could be the determining factor in your level of persistence and even your success or failure.
Greg Pryor, who was a member of the 1985 World Champion Kansas City Royals, is the co-owner of Life Priority, Inc. He works with dietary supplement ingredient manufacturers and research-scientists to bring high-quality, research-based dietary supplement ingredients and formulas to the marketplace.