Discussion Board » Clinical Trials » "Glycine Improves Memory" and "Glycine Improves the Quality of Sleep"

"Glycine Improves Memory" and "Glycine Improves the Quality of Sleep"

onward

Posted: Wednesday, November 14, 2012 10:47 PM

Joined: 12/20/2011
Posts: 217

Glycine Improves Memory

Both animal and human studies show that N-methyl-D-aspartate receptor function is involved in learning and memory. Glycine binds to a modulatory site on the NMDA receptor complex and, by increasing its function, may improve memory and learning.

This placebo-controlled, double-blind, manufacturer-supported study compared the effect on memory and attention of a single sublingual dose of 100 mg of an orally active form of glycine (Bioglycin) versus placebo in 30 medical students (mean age, 21; 15 females) and 18 middle-aged professional males (mean age, 59).

Participants were tested before and after administration of glycine and the placebo. At baseline, the older group showed poorer verbal episodic memory, as well as poorer focused, divided, and sustained attention. The glycine compound significantly improved both visual and verbal episodic memory retrieval in both groups, had no effect on focused or divided attention, and significantly improved sustained attention in only the older group.

Comment: In this study, decreased cognitive function was not required for glycine's beneficial effect in a selected group of highly educated individuals. The effects were not uniform across tests that had age-related baseline differences, implying that age also is not a factor. The improved recall of words that had been presented before administration of the compound suggests that glycine's main effect is to improve memory recall and thus is fundamentally different from the effect of more familiar cognitive enhancers such as caffeine, nicotine, and amphetamine, which improve only attention.

http://psychiatry.jwatch.org/cgi/content/full/2000/201/12

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J Clin Psychopharmacol. 1999 Dec;19(6):506-12.

Beneficial effects of glycine (bioglycin) on memory and attention in young and middle-aged adults.

File SE, Fluck E, Fernandes C.

Source:
Psychopharmacology Research Unit, United Medical and Dental Schools of Guy's and St Thomas' Hospitals, Guy's Hospital, London, United Kingdom. sandra.file@kcl.ac.uk

Abstract

The N-methyl D-aspartate receptor complex is involved in the mechanism of long-term potentiation, which is thought to be the biological basis of learning and memory. This complex can be manipulated in a number of ways, one of which is through the strychnine-insensitive glycine receptor coagonist site.

The effects of Bioglycin(Konapharma, Pratteln, Switzerland), a biologically active form of the amino acid glycine, were therefore studied in healthy students (mean age, 20.7 years) and middle-aged men (mean age, 58.9 years) with tests that measured attention, memory and mood, using a double-blind, randomized, crossover design.

Compared with the young group, the middle-aged group had significantly poorer verbal episodic memory, focused, divided, and sustained attention; they also differed in their subjective responses at the end of testing.

Bioglycin significantly improved retrieval from episodic memory in both the young and the middle-aged groups, but it did not affect focused or divided attention. However, the middle-aged men significantly benefited from Bioglycin in the sustained-attention task.

The effects of Bioglycin differed from those of other cognitive enhancers in that it was without stimulant properties or significant effects on mood, and it primarily improved memory rather than attention.

It is likely to be of benefit in young or older people in situations where high retrieval of information is needed or when performance is impaired by jet lag, shift work, or disrupted sleep.

It may also benefit the impaired retrieval shown in patients with schizophrenia, Parkinson's disease, and Huntington's disease.

PMID: 10587285

http://www.ncbi.nlm.nih.gov/pubmed/10587285

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New Therapeutic Strategy for Amino Acid Medicine:

Glycine Improves the Quality of Sleep

Makoto Bannai and Nobuhiro Kawai1

Frontier Research Laboratories, Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Kanagawa 210-8681, Japan

Received July 24, 2011; Accepted September 24, 2011

Abstract.

Glycine is a non-essential amino acid that has indispensable roles in both excitatory and inhibitory neurotransmission via N-methyl-D-aspartate type glutamate receptors and glycine receptors, respectively. We recently reported that glycine ingestion before bedtime significantly ameliorated subjective sleep quality in individuals with insomniac tendencies. Oral administration of glycine to rats was found to induce a significant increase in the plasma and cerebrospinal fluid glycine concentrations and a significant decrease in the core body temperature associated with an increase in cutaneous blood flow. The decline in the core body temperature might be a mechanism underlying glycine’s effect on sleep, as the onset of sleep is known to involve a decrease in the core body temperature. Moreover, a low core body temperature is maintained during sleep in humans. Pharmacological studies investigating the mechanisms of glycine on sleep were also performed. In this review, we will describe both our recent findings regarding how and where orally administered glycine acts and findings from our rat study and human trials.

... Insomnia is known to induce cognitive inefficiency, sleepiness, mood disruptions, impaired attention, and memory deficits...

Glycine and sleep in humans

We have previously reported three human volunteer

studies to subjectively assess the effect of glycine on

sleep.

Individuals with continuous complaints about the

quality of their sleep were recruited and given either 3 g

of glycine or a placebo before bedtime. In the first study

(4), a randomized double-blinded crossover trial, 19 female

volunteers (24 – 53 years of age; average, 31.1

years) participated. All of the subjects had complained

about their sleep quality. Their Pittsburgh Sleep Quality

Index (PSQI) scores were 6 or greater, indicating that the

subjects had continuously experienced unsatisfactory

sleep. The subjective quality of sleep was evaluated using

the St. Mary’s Hospital (SMH) Sleep Questionnaire
(24) and the Space-Aeromedicine (SAM) Fatigue Checklist
(25). Glycine significantly improved the feeling of
fatigue the next morning, indicating that glycine helps
improve sleep quality.

The second study (5), a randomized single-blinded

crossover trial, included 11 volunteers (8 females and 3

males; 30 – 57 years of age; average, 40.5 years), whose

mean PSQI score was 8.07, indicating repeated unsatisfactory

sleep. Polysomnographic (PSG) examinations

were performed throughout the night, and the subjective

quality of sleep was evaluated using the SMH Sleep

Questionnaire. Furthermore, daytime sleepiness was assessed

at 08:00, 10:00, 12:00, 21:00, and 23:00 on the
day following the examination. The PSG examinations

revealed a stabilized sleep state and a shortened latency

to both the sleep onset and slow-wave sleep, with no alterations

in the sleep architecture. Glycine also subjectively

improved the volunteers’ satisfaction with their

sleep, the difficulty of sleep onset, and sleep efficiency.

Furthermore, daytime sleepiness was significantly improved

in the morning, as measured by the Visual

Analogue Scale (26). Taken together, these findings indicate

that glycine improves sleep quality both subjectively

and objectively.

No serious side effects have been observed with the

administration of 31 g/day of glycine (27). The third trial

investigated any acute adverse events and daytime

sleepiness after the administration of 9 g of glycine. This

study was an open trial because any safety problems

needed to be addressed quickly if they occurred. A total

of 12 volunteers (6 females and 6 males; 25 – 39 years of

age; average, 34.0 years) participated in the study. Their

mean PSQI score was 4.41, indicating no particular

problems regarding sleep. Glycine (9 g) administered
during the day did not induce sleepiness and had no adverse

effects. Together, the results of these three aforementioned

human trials indicate that glycine improves

sleep quality in a subjective and objective manner and

has no serious adverse effects...

https://www.jstage.jst.go.jp/article/jphs/118/2/118_11R04FM/_pdf

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Top food sources of Glycine:
http://foodinfo.us/SourcesUnabridged.aspx?Nutr_No=516

"Gelatin is unusually high in the non-essential amino acids glycine and proline"
http://en.wikipedia.org/wiki/Gelatin

(A caveat about gelatin... Never microwave gelatin. Some sources say that microwaved gelatin can have adverse effects on health.)

Serenoa

Posted: Thursday, November 15, 2012 8:28 AM

Joined: 4/24/2012
Posts: 484

Very interesting. It's another clue to this mystery. I remember Lane also referencing NMDA and peroxynitrites in previous posts, "Peroxynitrites also nitrate NMDA receptors leading to the efflux of glutamate and the influx of calcium which kills brain cells."

onward

Posted: Thursday, November 15, 2012 9:16 PM

Joined: 12/20/2011
Posts: 217

A few other things I came across, re glycine:

Glycine

• Glycine modulates the NMDA deleterious effect receptors thereby increasing cognitive functions. NMDA is a brain receptor which requires glycine to activate it and is responsible for taking in an electrical response and converting it to a chemical neurotransmitter

• Inhibiting glycine with MAO inhibitors has a deleterious effect on memory formation

• In laboratory animals blocking the glycine site caused memory impairment but when unblocked reversed the visual recognition memory deficits.

• In a Swiss randomized, doubled blinded crossover study the effects of glycine on memory and attention in both young students (mean age 20) and middle aged (mean age 59) were evaluated. In the pre-study the middle aged subjects had poorer verbal memory and attention. Glycine improved memory retrieval in both young and middle aged but had no effect on attention. Glycine had no effect on mood, no stimulatory properties and primarily improved memory rather than attention.

- Dr. Michael Murray

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SunshineFour

Posted: Friday, November 16, 2012 12:19 PM

Joined: 12/29/2011
Posts: 17

thanks for this, I have been looking at buying for my parent this Whey protein drink as someone has written a positive review after their mother took it, this drink contains Glycine. Please see below review which is still on the iherb.com website

Bluebonnet Nutrition, Multi-Action Whey of Life Whey Protein, Natural Chocolate Blitz Flavor, 2.2 lbs (1008 g)

Alzheimer's supplementation protocol we tried Jul 26, 2011

This product was purchased by Reviewer1307319 from Great Britain

A recent pilot study (P.Scheltens et al, Alzheimers & Dementia, (2010)1-10) looked at whether degeneration due to alzheimers is arrestable and the brain can build new synapses and dendrites. The study included the nucleotide uridine which enhances synaptic growth and was part of a protocol including other supplements. After 12 weeks there was clear improvement in memory in the alzheimers patients on the trial. We decided to try the protocol including this whey protein (which contains uridine) for my mother (age 79) who shows early signs of the illness. After six months can only say the change in memory function has been amazing - so we very much concur with the findings of the trial. I know studies are ongoing looking at the long term affect of supplementation - that'll take time - for us it is worth making this part of Mum's regime now - added bonus it's delicious too!

http://www.iherb.com/product-reviews/Bluebonnet-Nutrition-Multi-Action-Whey-of-Life-Whey-Protein-Natural-Chocolate-Blitz-Flavor-2-2-lbs-1008-g/13590/?p=2&lang=en

onward

Posted: Friday, November 16, 2012 2:21 PM

Joined: 12/20/2011
Posts: 217

SunshineFour, thanks very much for your post!

The reviewer at iHerb makes mention of a scientific study. I think it may have been a study for a medical food called SOUVENAID. As you may know, there have been occasional encouraging reports about Souvenaid for a while now, but I don't think it's available in the U.S. yet.

So this is very interesting that someone claims to have seen very positive results using a similar product - one that's readily available at iHerb and Amazon.com

It's not clear to me whether the reviewer at iHerb used just that one product (Bluebonnet Nutrition, Multi-Action Whey of Life Whey Protein, Natural Chocolate Blitz Flavor) or other things too. [The reviewer says: "We decided to try the protocol including this whey protein (which contains uridine)..."]

In any case, I think this may be the study that the reviewer at iHerb was referring to:

Efficacy of a medical food in mild Alzheimer's disease: A randomized, controlled trial.

Scheltens P, Kamphuis PJ, Verhey FR, Olde Rikkert MG, Wurtman RJ, Wilkinson D, Twisk JW, Kurz A.

Source

VU University Medical Center, Amsterdam, The Netherlands. p.scheltens@vumc.nl

Abstract

OBJECTIVE:

To investigate the effect of a medical food on cognitive function in people with mild Alzheimer's disease (AD).

METHODS:

A total of 225 drug-naïve AD patients participated in this randomized, double-blind controlled trial. Patients were randomized to active product, SOUVENAID, or a control drink, taken once-daily for 12 weeks. Primary outcome measures were the delayed verbal recall task of the Wechsler Memory Scale-revised, and the 13-item modified Alzheimer's Disease Assessment Scale-cognitive subscale at week 12.

RESULTS:

At 12 weeks, significant improvement in the delayed verbal recall task was noted in the active group compared with control (P = .021). Modified Alzheimer's Disease Assessment Scale-cognitive subscale and other outcome scores (e.g., Clinician Interview Based Impression of Change plus Caregiver Input, 12-item Neuropsychiatric Inventory, Alzheimer's disease Co-operative Study-Activities of Daily Living, Quality of Life in Alzheimer's Disease) were unchanged. The control group neither deteriorated nor improved. Compliance was excellent (95%) and the product was well tolerated.

CONCLUSIONS:

Supplementation with a medical food including phosphatide precursors and cofactors for 12 weeks improved memory (delayed verbal recall) in mild AD patients. This proof-of-concept study justifies further clinical trials.

PMID: 20129316 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/20129316

See the full paper here:
http://modernedementiezorg.nl/upl/eten_en_drinken/Scheltens%20et%20al%20Alzheimers%20Dement%202010%206%201-10.pdf

onward

Posted: Friday, November 16, 2012 2:33 PM

Joined: 12/20/2011
Posts: 217

Bluebonnet Nutrition, Multi-Action Whey of Life Whey Protein, Natural Chocolate Blitz Flavor

Below is a link to a page that shows the long list of this product's ingredients. (I tried to paste the information here but the formatting got hopelessly messed up.)

http://www.iherb.com/Bluebonnet-Nutrition-Multi-Action-Whey-of-Life-Whey-Protein-Natural-Chocolate-Blitz-Flavor-2-2-lbs-1008-g/13590

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And here's an article I just came across that lists the ingredients of Souvenaid and suggests how to obtain them through supplements and foods:

http://gaia-health.com/gaia-blog/2012-07-27/ease-alzheimers-with-prescription-only-medical-food-or-eat-real-food-avoid-it/

According to the above article which is dated July 2012, Souvenaid is expected to be available in the U.S. "next year" (2013) - but it will be available by prescription only.

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It looks to me like Souvenaid contains a number of ingredients not found in the Bluebonnet Nutrition Multi-Action Whey of Life Whey Protein, but those missing ingredients could be gotten from additional supplements.

I wish that the reviewer at iHerb had listed the entire protocol that he or she tried with such great success.

Lane Simonian

Posted: Wednesday, November 21, 2012 10:30 AM

Joined: 12/12/2011
Posts: 5085

It's interesting that the whey product includes glycine, glutamaric acid, and cystine/cysteine as these are the three components of glutathione which is the body's chief defense against peroxynitrites and other oxidants. Glutathione supplements are likely of little use, because apparently glutathione cannot get into cells on its own. Problems in cystine transport may also limit the effectiveness of cystine supplementation.

I am interested in the comment that glycine "modulates the NMDA deleterious effect receptors thereby increasing cognitive function." Depending on the mechanism, this may be helpful. Ironically, the activation of the NMDA receptor increases the release of acetylcholine which is needed for short-term memory, but the overactivation of this receptor leads to the excess release of acetylcholine (thus in part the overexcitation of neurons during the early stages of Alzheimer's disease). And this process, eventually leads to the death of neurons.

Inhibit and possibly reverse the peroxynitrite-mediated nitration of NMDA receptors and this process can be slowed down at least.