Ingredients in the sleepscape complex (4 of 5)

Taurine:
Important Brain Nutrient

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

By Durk Pearson & Sandy Shaw

T aurine 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. (See “GABA in the SleepScape” in the April 2013 issue of Life Enhancement magazine.)

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. Neurosci. 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 Neuroinflammation. 1(1):22 (2004).

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