Category: Productive Sleep

Life Priority, Inc. Introduces Durk Pearson & Sandy Shaw’s®

PRODUCTIVE 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.  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: Glycine, GABA, Choline, 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.

GABA

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.

References

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).

2. 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).

3. 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).
4. 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.

 

 

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 mice^3A 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 paper^9B 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.

STRESS, STRESS, STRESS RELIEVED BY THEANINE

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!

References

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.

References

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.