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  1. #1
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    A group of Japanese researchers are doing some interesting work on l-glycine supplementation as a treatment for insomnia. Any thoughts on the potential for this? There's no one else that I could find that's doing this research.



    Also, I have the full text of their preliminary 2006 paper, but not the new 2007 one. I was wondering if anyone has access to this latter full journal article?

    http://www.blackwell-synergy.com/doi/abs/1...25.2007.00262.x



    Subjective effects of glycine ingestion before bedtime on sleep quality

    Authors: INAGAWA, Kentaro; HIRAOKA, Takenori1; KOHDA, Tohru1; YAMADERA, Wataru2; TAKAHASHI, Michio3

    Source: Sleep and Biological Rhythms, Volume 4, Number 1, February 2006 , pp. 75-77(3)



    The effects of glycine on sleep quality were examined in a randomized double-blinded cross-over trial. The volunteers, with complaints about the quality of their sleep, ingested either glycine (3 g) or placebo before bedtime, and their subjective feeling in the following morning was evaluated with the St. Mary's Hospital Sleep Questionnaire and Space-Aeromedicine Fatigue Checklist. The glycine ingestion significantly improved the following elements: "fatigue", "liveliness and peppiness", and "clear-headedness". These results suggest that glycine produced a good subjective feeling after awakening from sleep.


    Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes

    Authors: Wataru YAMADERA, Kentaro INAGAWA, Shintaro CHIBA, Makoto BANNAI, Michio TAKAHASHI, Kazuhiko NAKAYAMA

    Source: Sleep and Biological Rhythms 5 (2), 126-131, April 2007



    In human volunteers who have been continuously experiencing unsatisfactory sleep, effects of glycine ingestion (3 g) before bedtime on subjective sleep quality were investigated, and changes in polysomnography (PSG) during sleep were analyzed. Effects on daytime sleepiness and daytime cognitive function were also evaluated. Glycine improved subjective sleep quality and sleep efficacy (sleep time/in-bed time), and shortened PSG latency both to sleep onset and to slow wave sleep without changes in the sleep architecture. Glycine lessened daytime sleepiness and improved performance of memory recognition tasks. Thus, a bolus ingestion of glycine before bedtime seems to produce subjective and objective improvement of the sleep quality in a different way than traditional hypnotic drugs such as benzodiazepines.


    --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



    I find this interesting because there's new research (that's very hot, published in Nature) that implicates Glycine in sleep paralysis (your body automatically paralyzes itself during REM sleep so you don't act out your dreams). Here are some quotes:



    http://www.nature.com/nature/podcast/v441/...2006-06-01.html

    "Jun Lu: It's very interesting. So what we found is that three groups of neurons are activated in REM sleep. One group projects to the forebrain and those cells contain excitory neurotransmitters. So you can imagine, when these cells become activated they project to the forebrain and your brain becomes highly activated.



    Chris Smith: So what's that, glutamate or something?



    Jun Lu: It contains glutamate. And also there's another group of cells projects spinal cord and they also contain glutamate. But these cells don't project to the motor neuron directly. And they project to the interneuron. Those interneurons contain an inhibitory neurotransmitter, glycine.



    Chris Smith: So that's the correlate of how you become paralysed during sleep.



    Jun Lu: Exactly, so when these cells become activated you stimulate a glycine inhibitor in the neuron and that neuron shuts down the motor neuron, that's how you become paralysed."


    http://www.nature.com/neuro/journal/v9/n6/...606-721.html#B3

    "Neuronal recording studies in the cat and dog have identified a population of neurons in the medial medulla of the cat and dog that are active only during periods of muscle tone suppression14, that is, REM sleep and cataplexy. Stimulation of these cells suppresses muscle tone by release of GABA and glycine, and lesioning this region reduces the normal muscle tone suppression of REM sleep"
    Sonic @ May 19 2009, 01:02 PM:
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    weve been talking about this over in the bneta alanine thread. beta alanine may work similarly so we were looking at combining it with glycine / magnesium glycinate and glutamine.
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    Senior Member deekz's Avatar
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    GLYCINE: SYNTHESIS AND UPTAKE



    Glycine is the major inhibitory neurotransmitter in the brainstem and spinal cord, where it participates in a variety of motor and sensory functions. Glycine is also present in the forebrain, where it has recently been shown to function as a coagonist at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. In the latter, context glycine promotes the actions of glutamate, the major excitatory neurotransmitter (for a discussion of glycine's role as a coagonist of the NMDA receptor, see Excitatory Amino Acid Neurotransmission). Thus, glycine subserves both inhibitory and excitatory functions within the CNS.



    Glycine is formed from serine by the enzyme serine hydroxymethyltransferase (SHMT). Glycine, like GABA, is released from nerve endings in a Ca2+-dependent fashion. The actions of glycine are terminated primarily by reuptake via Na+/Cl--dependent, high-affinity glycine transporters. The specific uptake of glycine has been demonstrated in the brainstem and spinal cord in regions where there are also high densities of inhibitory glycine receptors.



    Recently, two glycine transporters have been cloned and shown to be expressed in the CNS as well as in various peripheral tissues (11, 19). These glycine transporters are members of the large family of Na+/Cl--dependent neurotransmitter transporters, and both share approximately 50% sequence identity with the GABA transporters discussed above. The deduced amino acid sequence of both cDNAs predicts the typical 12 transmembrane domains characteristic of these transporters. The two glycine cloned transporters have been named GLYT-1 and GLYT-2 in the order that they were reported (11). These transporter cDNAs are transcribed from the same gene and are quite similar in their 3¢ nucleotide sequences. They differ in their 5¢ noncoding regions as well as in the first 44 nucleotides of their coding sequence. Expression of GLYT-1 and GLYT-2 yield transporters with similar kinetic and pharmacological properties. Interestingly, however, the distribution of GLYT-1 and GLYT-2 transcripts measured by in situ hybridization are different. GLYT-1 mRNA also closely parallels the distribution of the glycine receptor. These data suggest that GLYT-1 is primarily a glial glycine transporter whereas GLYT-2 is primarily a neuronal transporter. The mapping of both glycine transporter mRNAs, as well as the glycine receptor subunit mRNAs, confirm the importance of this neurotransmitter in the brainstem and spinal cord, but support a more widespread distribution in supraspinal brain regions than was previously suspected.



    GLYCINE RECEPTORS



    Inhibitory glycine receptors are blocked by the plant alkaloid strychnine, which was also first used to label glycine receptors in spinal cord membranes (52, 53). Strychnine poisoning results in muscular contractions and tetany as a result of glycinergic disinhibition and overexcitation. Electrophysiological studies primarily carried out in rodent spinal cord neurons have demonstrated that glycine activates Cl- ion conductance (8). Like GABA, this increase in Cl- ion conductance results in a hyperpolarization of the neuronal membrane and an antagonism of other depolarizing stimuli. Other a- and b-amino acids, including b-alanine and taurine, also activate glycine receptors, but with lower potency (6, 8).



    The glycine receptor was first successfully solubilized and purified by Betz and colleagues using affinity purification over an affinity matrix derivatized with aminostrychnine (8). The affinity-purified glycine receptor was shown to consist of two polypeptide subunits of approximately 48 kD (a) and 58 kD (, respectively. Reconstitution of these polypeptide subunits into lipid vesicles resulted in functional receptors, and intramolecular cross-linking experiments suggested that the native glycine receptor is a pentameric structure. Photoaffinity labeling of the glycine receptor with [3H]strychnine revealed that both the strychnine and glycine binding sites are located on the 48-kD a subunit. Purification of the a-and b-receptor subunits was followed closely by their molecular cloning (7).



    The deduced amino acid sequences of the a- and b-glycine-receptor subunits predict structures quite homologous to the subunits of other ligand-gated ion channels, including the GABAA receptor (7). Each subunit has four hydrophobic membrane-spanning sequences, and each shares considerable sequence identity with the other. Several glycine-receptor a-subunit variants have now been identified (a1–4), and, not surprisingly, they differ in their pharmacological properties and level of expression. As mentioned, both the agonist and antagonist binding sites are located on the a subunit, but at different amino acids (50). Interestingly, glycine receptors comprised of a1 subunits are efficiently gated by taurine and b-alanine, whereas a2-containing receptors are not (8). The a1 and a2 genes are expressed in the adult and neonatal brain, respectively. Interestingly, the b-subunit transcript is expressed at relatively high levels in the cerebral cortex and cerebellum, where no a transcripts or specific [3H]strychnine binding sites have been observed. Coexpression of b subunits with a subunits (as opposed to homo-oligomeric a-subunit glycine receptors) results in glycine receptors with pharmacological properties quite similar to native glycine receptors. Nonetheless, the widespread distribution of b-subunit mRNA in brain suggests that other, perhaps strychnine-insensitive glycine receptor isoforms will be found.



    Recently, the expression of a1 and a2 subunits has been shown to be developmentally regulated with a switch from the neonatal a2 subunit (strychnine-insensitive) to the adult a1 form (strychnine-sensitive) at about 2 weeks postnatally in the mouse (8). The timing of this "switch" corresponds with the development of spasticity in the mutant spastic mouse (5), prompting speculation that insufficient expression of the adult isoform may underlie some forms of spasticity.



    CONCLUSIONS



    A convergence of scientific effort—involving molecular pharmacologists, molecular biologists, and medicinal chemists—has revealed a remarkable and, for the most part, unsuspected degree of complexity and heterogeneity in the biosynthetic enzymes, transporters, and receptors for GABA and glycine. For the neuropsychopharmacologist, GABA and glycine-containing and receptive neurons are of particular significance because they are among the best-characterized of all drug targets. Many psychoactive drugs which alter (increase or decrease) CNS excitability do so by effecting GABAergic or glycinergic neurotransmission. Some of these drugs (e.g., benzodiazepine and nonbenzodiazepine anxiolytic–hypnotics) are commonly prescribed for a variety of disorders. It is likely that the wealth of new information on GABA and glycine will result in an even better understanding of their potential role(s) in various neuropsychiatric disorders and in the discovery even more of effective therapeutic agents.



    Taken from:

    GABA and Glycine

    Steven M. Paul


    http://www.acnp.org/G4/GN401000008/Default.htm



    very interesting read..

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    Why beta alanine instead of glycine? Beta alanine is supposed to be much weaker than Glycine, and Glycine already has two publications in support of its use as a sleep aid...
    Sonic @ May 19 2009, 01:02 PM:
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    Senior Member ziddy's Avatar
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    What dosage? How long before bed? Full or empty stomach? Sublingual or oral?
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    Quote Originally Posted by ziddy' post='418247' date='Aug 16 2007, 10:45 AM
    What dosage? How long before bed? Full or empty stomach? Sublingual or oral?




    The initial post said 3 grams, and im assuming from the rest of the study that its on an empty stomach, right before getting into bed, and oral.
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    Senior Member Proton Soup's Avatar
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    interesting stuff. anyone know if this doctoral thesis is available, preferably in english?

    http://prensa.ugr.es/prensa/research/verNo...sa.php?nota=468

    05/07/2007



    Taking a supplement of glycine, a food additive, helps to prevent degenerative diseases such as arthrosis or osteoporosis



    - A doctoral thesis presented in the UGR has established that these diseases are due to a lack of this amino acid which is present in food such as fish, meat or dairy products.

    - The research, which was carried out at the Cellular Metabolism Institute in Tenerife, studied the effect of the glycine supplement in the diet of a group of 600 volunteers affected by different diseases related to the mechanical structure of the organism.

    C@MPUS DIGITAL Glycine is a non-essential amino acid used by the organism to synthesise proteins and is present in foods such as fish, meat or dairy products. The study, carried out at the Cellular Metabolism Institute in Tenerife and at the Department of Biochemistry and Molecular Biology of the University of Granada by Doctor Patricia de Paz Lugo and supervised by Doctors Enrique Meléndez Hevia, David Meléndez Morales and José Antonio Lupiáñez Cara, established that the direct intake of this substance as a food additive helps to prevent arthrosis and other degenerative diseases, in addition to other diseases related to a weakness in the mechanical structure of the organism, including the difficulty of repairing physical injuries.



    The work of De Paz Lugo was developed at the Cellular Metabolism Institute (CMI) in Tenerife, where researchers studied the effect of the glycine supplement on the diet of a group of 600 volunteers affected by different diseases related to the mechanical structure of the organism such as arthrosis, physical injuries or osteoporosis. The patients analysed were aged 4-85, and the average age was 45.



    In all cases, there was a notable improvement in the symptomology. “Thefore –according to De Paz Lugo- we concluded that many degenerative diseases such as arthrosis can be treated as deficiency diseases due to the lack of glycine, since supplementing a diet with this amino acid leads to a notable improvement in symptomology without the need to take pain-killers”.



    A very common disease



    Arthrosis is the most common osteoarticulary problem in our society: more than 50% of the population suffer from it after the age of 65, and 80% of people over 75. It consists of a degeneration of the articulary cartilage which disappears until it leaves the subchondral bone exposed. Arthrosis has no cure at present and the most widely used treatments are pain-killers and NSAID (non-steroidal antiinflammatory drugs), which only relieve pain but do not repair the damage in the cartilage or influence the development of the disease.



    The work carried out by the scientist from the CMI shows that collagen has a unique structure with a right-handed triple superhelix in which the glycine represents a third of its residues. Mathematical analysis of the metabolic route of the synthesis of the glycine, developed by the research group to which Patricia de Paz belongs, demonstrated that this amino acid should be considered an essential amino acid.



    The doctoral thesis carried out at the CMI and the UGR has shown that the capacity of the metabolism to synthesise glycine is very limited. The conclusion of this study is that glycine, administered in daily doses of 10 grams divided into two doses of 5 grams ?one in the morning and one at night? leads to a general improvement in these problems over a period of time which, in most cases, is between two weeks and four months.



    Reference: Dr. Patricia de Paz Lugo. Cellular Metabolism Institute, La Laguna (Tenerife) Phone: 922 315688. Mobile: 619953416. E-mail: patricia@metabolismo.es




    i saw that lef.org had it in their news a few days ago, and the press release from the university is about as close as i've gotten.



    i think the sleep connection is interesting because the study is saying that glycine should be treated as an essential amino acid because its production is limited. and apparently it gets even more limited as you get older. old people have as much trouble getting a good night's sleep as they do maintaining connective tissue. and now, i know there's a lot more things contributing to sleep problems than just this, but still interesting that two very different problems may be related.

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    Hello, here you have the Doctoral Thesis (in Spanish):
    http://hera.ugr.es/tesisugr/16442349.pdf
    If you need more information, please do not hesitate to contact with me again.



    <div class='quotetop'>QUOTE (Proton Soup @ Aug 18 2007, 02:20 AM) <{POST_SNAPBACK}></div><div class='quotemain'>interesting stuff. anyone know if this doctoral thesis is available, preferably in english?
    http://prensa.ugr.es/prensa/research/verNo...sa.php?nota=468



    i saw that lef.org had it in their news a few days ago, and the press release from the university is about as close as i've gotten.

    i think the sleep connection is interesting because the study is saying that glycine should be treated as an essential amino acid because its production is limited. and apparently it gets even more limited as you get older. old people have as much trouble getting a good night's sleep as they do maintaining connective tissue. and now, i know there's a lot more things contributing to sleep problems than just this, but still interesting that two very different problems may be related.</div>

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    Seeing how ketamine and other NMDA antagonists cause insomnia, this makes sense.

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    Quote Originally Posted by SoulSeeker View Post
    Also, I have the full text of their preliminary 2006 paper, but not the new 2007 one. I was wondering if anyone has access to this latter full journal article?

    http://www.blackwell-synergy.com/doi/abs/1...25.2007.00262.x


    Better late than never right?
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    Thanks Funk. This may be just the ticket for my wife.



    An additional benefit of ingesting Glycine (if my memory serves me correctly) is its supposed involvement in the safe removal of petro chemicals or Benzenes from the body? I'd have to hunt for something to back this up though..

  12. #12
    Senior Member Tussmann's Avatar
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    Anybody got cheaper alternatives to this?

    http://www.swansonvitamins.com/SWU515/ItemDetail?n=0

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    Quote Originally Posted by Tussmann View Post
    Anybody got cheaper alternatives to this?

    http://www.swansonvitamins.com/SWU515/ItemDetail?n=0


    And I thought I was a tightwad.

    Seriously though, you're not going to find much cheaper than that. At 3 grams a day that will last 2 1/2 months...Only having to pay ~$2 a month for any supplement is pretty good.
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    Senior Member FunkOdyssey's Avatar
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    Quote Originally Posted by ((Vibe)) View Post
    And I thought I was a tightwad.

    Seriously though, you're not going to find much cheaper than that. At 3 grams a day that will last 2 1/2 months...Only having to pay ~$2 a month for any supplement is pretty good.


    lol, yeah that's what I was thinking when I saw that swanson price.
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    Senior Member Tussmann's Avatar
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    Quote Originally Posted by ((Vibe)) View Post
    And I thought I was a tightwad.

    Seriously though, you're not going to find much cheaper than that. At 3 grams a day that will last 2 1/2 months...Only having to pay ~$2 a month for any supplement is pretty good.


    I'm a poor college kid and it doesn't seem like there's enough anecdotal reports in this thread. If I'm going to try this out, it better be cheap. After accounting for shipping/handling it will run me probably 12 bucks. That is not cheap for something that might not work.

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    Quote Originally Posted by Tussmann View Post
    I'm a poor college kid and it doesn't seem like there's enough anecdotal reports in this thread.




    I always find the reviews on iherb helpful for this.




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    Quote Originally Posted by Odium View Post
    I always find the reviews on iherb helpful for this.


    Is it just me, or do the iherb reviewers tend to inflate their scores? I don't think there is any sort of scam going on, but scores in general just seem too high. Also, I rarely find any thoughtful, negative reviews there.



    But back to the subject at hand: I can't say I've ever noticed a profound difference in sleep quality, but glycine did help calm me down and induce sleep when necessary.



    Also, if you can't find anecdotal reports here, it never hurts to check out the imminst forums (recently renamed and now here). I haven't visited lately, but it used to be a quality forum.

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    Nice to see an old thread of mine resurface.

    I can provide my anecdotal experience:



    L-Glycine doesn't really work like a "hypnotic" in that it will not knock you out. In my past experience, it seems to have a very mild relaxant effect that eases the way into sleep. I can't tell if it increased my sleep quality, but I tried taking a teaspoon in conjunction with 0.25mg of melatonin on some nights when I've had mild insomnia and it has tended to help. I think this is a great combo, especially since I advocate avoiding the z-hypnotics (e.g. ambien) if possible. I generally recommend trying the OTC approach first, and resorting to the prescription drugs as needed.



    I also want to highlight that CBT for insomnia (CBTi) has consistently been shown to outperform medication treatment, especially in the long-term. Ultimately, sleep hygiene and behavioral techniques are the way to go to address insomnia, and pharmacological solutions should only be used transiently or on rare occasions.
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    Re: Ксения

    Я бы не хотел развивать эту тему.


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    Glycine is a conditionally essential amino acid that serves as an inhibitory and excitatory neurotransmitter.It has been shown to enhance endurance and energy levels.It has received attention recently as a potential treatment for other maladies.It is a non-essential amino acid. Tell us your experience with L-Glycine for fibromyalgia.

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