Glycine and Slow Wave Sleep

A recent study on sleep and dementia points out (once again) that sleep is essential for good health in aging. The study discovered that getting less sleep in your 50s and 60s, such as 6 hours or fewer per night, raises your risk of dementia in your later years by 30%.[ref][ref]

Quality sleep is foundational for health and longevity

Sleep is one of those essential things that everyone should prioritize to maintain good health. Yes, rare mutations reduce your need for sleep, but if you’re not one of the 1 in 10,000 people with the DEC2 mutation, you need to get around 7.5 to 8 hours of sleep per night.

How can you improve sleep quality? 

Of course, the first step is to plan enough time for sleep. Parents of small children understand the importance of getting enough sleep. However, as adults, we tend to overlook the simple math on this. I was surprised when my Oura ring prompted me to start getting ready for bed at 9:15 p.m. However, because I usually get up at about 5:45 a.m., Oura was simply deducting 8 hours and adding a half-hour buffer to brush my teeth and wind down to sleep.

Sleep duration is a straightforward metric… But everyone knows that poor quality sleep negatively impacts how you feel the next day. Slow wave sleep is a key here.

Your brain activity goes through multiple stages when you sleep. You will have segments of light sleep, REM sleep, and slow-wave sleep.

Why is slow wave sleep important?

More slow-wave sleep is linked to better response time and accuracy in cognitive tests the next day.[ref]

One of the problems with aging is that slow-wave sleep decreases and becomes more fragmented. Researchers think this loss of slow-wave sleep is thought to cause cognitive decline and lead to higher amyloid-beta levels (Alzheimer’s implications).[ref][ref]

The contrary is also true, with research indicating that getting more slow-wave sleep can help avoid cognitive decline. Animal research points to a possible benefit for Alzheimer’s prevention with solid slow-wave sleep.[ref]

How can you increase your slow-wave sleep?

Glycine before bed may help increase your sleep quality and the time spent in slow-wave sleep.

Glycine is an amino acid used throughout the body in many different ways. Your body naturally produces glycine (avg. of 45g per day), and you also get some from your diet (avg. 3-5g per day).

In the central nervous system, glycine acts as an inhibitory neurotransmitter via glycine receptors in certain types of neurons. Additionally, glycine and glutamate act together in the brain in certain types of excitatory neurons.[ref]

So what is going on in the brain when you take glycine at night?

When taking glycine as a supplement, it can easily pass across the blood-brain barrier to be used in the brain.

Glycine is a co-agonist with glutamate as a neurotransmitter in some regions of the brain. NMDA receptors in neurons are activated by glutamate and glycine when certain conditions are met. (The NMDA receptors also activate with certain psychoactive drugs, ketamine, and alcohol.)[ref]

One area of the brain with NMDA receptors is the suprachiasmatic nucleus, the region of the hypothalamus responsible for your circadian rhythm. Animal research shows that activation of these NMDA receptors by glycine decreases body temperature at night and is sleep-promoting.[ref]

Some people naturally get more slow wave sleep:

Genetics plays a role in how much slow wave sleep you naturally get. There are a couple of different genes that are important here.

Adenosine levels drop as you sleep:

During the day, adenosine builds up in your brain as your brain uses ATP (adenosine triphosphate) for energy. The ATP molecule gives up a phosphate to generate energy from the chemical bond. ADT (adenosine diphosphate) is formed, which can then give up another phosphate to form AMP (adenosine monophosphate).

One way the body can control adenosine levels is to convert them to inosine using the enzyme adenosine deaminase (ADA). This enzyme is used in the brain to decrease adenosine levels as you sleep.[ref] As adenosine levels drop throughout the night, the pressure to sleep also decreases.[ref]

While researchers have known for a while that adenosine is important in feeling sleepy, recent animal studies have clearly shown that activation of the adenosine receptor, ADORA2A, by the adenosine molecule induces slow-wave sleep.[ref]

BDNF and Sleep:

BDNF (brain-derived neurotrophic factor) acts on synaptic connections between neurons in the brain, potentiating or increasing them. One of BDNF’s functions is to aid neuroplasticity and memory formation.

Related article: The Interaction Between BDNF and Serotonin

BDNF appears to play a role in slow-wave sleep as well. Low BDNF levels are linked to sleep disturbances and an increased risk of depression.[ref]

Research ties glycine and BDNF together in relation to slow-wave sleep. Animal studies show that BDNF alters glycine uptake by impacting the way glycine transporters work in the neurons.[ref]


Slow Wave Sleep Genotype Report:

People with genetic variants in the ADA gene get more slow wave sleep on average than normal, while BDNF variants can lead to decreased slow wave sleep.

The ADA gene codes for adenosine deaminase, an enzyme that converts adenosine into inosine.

Check your genetic data for rs73598374 G22A (23andMe v4, v5; AncestryDNA):

  • C/C: typical clearance of adenosine
  • C/T: reduced clearance of adenosine, fewer awakenings during the night[ref], more deep sleep, but may feel sleepy when waking up too soon[ref] increased Stage 1 and Stages 3-4 sleep[ref]
  • T/T: reduce clearance of adenosine, more deep sleep but may feel sleepy when waking up, increased Stage 1 and Stages 3-4 sleep

Members: Your genotype for rs73598374 is .

The BDNF gene codes for the brain-derived neurotrophic factor.

Check your genetic data for rs6265 (23andMe v4, v5; AncestryDNA):

  • T/T: decreased BDNF[ref] referred to in studies as Met/Met; averages over 20 minutes less of deep sleep[ref]
  • C/T: somewhat decreased BDNF, referred to as Val/Met; averages 20 minutes less of deep sleep[ref]
  • C/C: typical BDNF, referred to as Val/Val;

Members: Your genotype for rs6265 is .


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References:

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Aroeira, Rita I., et al. “BDNF Modulates Glycine Uptake in Hippocampal Synaptosomes by Decreasing Membrane Insertion of Glycine Transporter 2.” Neurochemistry International, vol. 99, Oct. 2016, pp. 94–102. ScienceDirect, https://doi.org/10.1016/j.neuint.2016.06.007.

Bachmann, Valérie, Federica Klaus, et al. “Functional ADA Polymorphism Increases Sleep Depth and Reduces Vigilant Attention in Humans.” Cerebral Cortex (New York, N.Y.: 1991), vol. 22, no. 4, Apr. 2012, pp. 962–70. PubMed, https://doi.org/10.1093/cercor/bhr173.

Bachmann, Valérie, Carina Klein, et al. “The BDNF Val66Met Polymorphism Modulates Sleep Intensity: EEG Frequency- and State-Specificity.” Sleep, vol. 35, no. 3, Mar. 2012, pp. 335–44. PubMed Central, https://doi.org/10.5665/sleep.1690.

Bannai, Makoto, et al. “The Effects of Glycine on Subjective Daytime Performance in Partially Sleep-Restricted Healthy Volunteers.” Frontiers in Neurology, vol. 3, 2012. Frontiers, https://www.frontiersin.org/article/10.3389/fneur.2012.00061.

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About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.