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Trouble sleeping? You’re not alone. Our modern society makes it hard for some people to get enough rest—whether it's lengthy work schedules, social engagements, or just a large amount of stress. Over 30% of people have some sort of insomnia-like symptoms and about the same number, approximately one-third of adults, don’t get the recommended 7 - 9 hours of sleep per night.

Lack of sleep is an issue because it increases the risk for many diseases, and also impairs mental and physical performance. In order to grind hard every day, you need your sleep.

Rather than resort to sleep medications or other alternative strategies to get to sleep (deep breathing, counting sheep, flipping the pillow over to the cooler side) there is an increasing interest in using natural compounds to promote a good night’s rest. Glycine has become a big player in the sleep-supplement realm. It may work wonders for you.

One Amino Acid with Many Roles

The amino acid glycine is mostly known for its biological activities related to the synthesis of collagen—the protein in our body that makes up connective tissue, bones, cartilage, blood vessels, and other structures. Glycine is what’s known as a non-essential amino acid—our body can make their own glycine.

Collagen is also often consumed in supplement form as peptides to support healthy bones, skin, hair, and nails plus vitamin C, copper, and zinc to support your own collagen production.

Glycine is also used to produce the blood protein heme, creatine, antioxidant molecules, and certain enzymes. To make all of these molecules and structures, our body can synthesize glycine on its own.

However, we still need to ingest a certain amount of dietary (or supplemental) glycine to ensure we have enough around.

Why is it important to get enough? Research shows that glycine is associated with some major health benefits.

People who get a higher amount of dietary glycine are shown to have better insulin sensitivity, less abdominal fat,Lustgarten2013 lower blood pressure, and fewer risk factors for cardiovascular events like a heart attack or stroke.Ding2015 Glycine supplementation can increase antioxidant levels, reduce inflammation,Sekhar2011 and even increase growth hormone levels when given in a single high dose,Kasai1980,Kasai1978 so it might even be good for exercise performance and muscle building. It’s a non-essential amino acid with some pretty “essential” roles.



A Starring Role in Sleep

Several of us resort to medications and other techniques to fall asleep. While natural sleep patterns are best, sometimes the brain needs a little bit of a chill pill (literally). Glycine might just be a fantastic stand-in for some typical sleep agents and come without some of the known side effects.

An Alternative to Sleep Aids

Several commercial sleep aids exist—from your traditional melatonin to other strong hypnotics. And yes, they do work, with most showing improvements in sleep quality, ability to fall asleep, and reduced sleep problems.

But, while over the counter or prescription sleeping pills will certainly induce sleep, they might not lead to the right kind of sleep. Certain hypnotics have been shown to induce alterations in various sleep cycles and sleep architecture, increase sleep latencyPagel2001 (the time taken to fall asleep) and even reduce sleep-dependent memory consolidation.HallPorter2014 They lead to a whole slew of other problems.

In one study where participants were dosed with 12g of a sleeping medication (Ambien) before bedtime, their scores the following day on tests of memory were significantly impaired.HallPorter2014 This study suggests that sleep medications can have short-term, detrimental effects on memory.

Sleeping pills also come with various side effects which may include appetite changes, constipation, dizziness, daytime drowsiness, gas, headache, daytime impairment, mental slowing, or unusual dreams. This is starting to sound like a pharmaceutical commercial. Many of these sound a lot worse than missing a few hours of shut-eye. A natural alternative without all of the above sounds pretty pleasing right about now.

How Glycine Promotes Sleep

To properly wind down at night, fully relax, and disengage from the outside world, we need to calm our central nervous system. Glycine might help this process by working its magic throughout the brain, leading to a deep, restful sleep.

Mind Game

Among its many roles, glycine acts like an inhibitory neurotransmitter in the central nervous system, participating in the processing of motor and sensory info, aiding movement, vision, and hearing. The glycine receptor can be inhibitory as well as an excitatory neurotransmitter, depending on the brain region where it resides.

When you think inhibitory, think “calming.” Indeed, a calming effect on the CNS is one reason glycine is being investigated in the area of sleep, with promising results. How does supplemental glycine nudge its way into our neurons?

When taken exogenously (i.e. as a supplement), glycine is actually able to cross the blood-brain barrier. Here, it builds up in the cerebrospinal fluid which flows throughout the brain, where it can then be distributed and act accordingly in different regions. One effect involves glycine activating what are known as NMDA receptors in the brain. NMDA receptors are excitatory, and known to be involved in important nervous system functions like synaptic plasticity, formation of new synapses important for memory and learning, as well as forming neural networks.

The brain is also where glycine works its inhibitory magic, perhaps working alone or alongside other inhibitory neurotransmitters like GABA to quiet down the nervous system.

When glycine binds to glycine receptors in the brain, it inhibits the firing of neurons, allowing the mind to feel more at ease and become less responsive to certain stimuli.

Another avenue by which glycine promotes sleep is by blocking receptors for the hormone orexin. Orexin is a peptide with a long history in our survival mechanisms, with roles such as maintaining energy homeostasis by promoting food-seeking behavior and other reward systems. Orexin also regulates wake and sleep cycles, mainly by maintaining arousal and helping us stay awake, alert, and attentive.Hondo2011 People who have a deficiency in orexin often suffer from narcolepsy—excessive sleepiness.

It turns out, Glycine actually prevents orexin neurons from firing—essentially making this hormone inactive and preventing the wake-promoting actions. This might play a role in helping you sleep, another reason why supplemental glycine may be sleep-promoting.

Keeping it Cool

The ability to fall asleep is partially dependent on a drop in body temperature at night. Cooler body temperatures are associated with sleep, and warmer temperatures the opposite. Sleep is governed, in large part, by the rhythm of your core body temperature—the faster you can cool down, the quicker you’ll fall asleep. If you’ve ever struggled to doze off on a hot summer night with broken air conditioning, this comes as no surprise.

Things like hypnotics and melatonin induce sleep by lowering body temperature; glycine also promotes sleep potentially through the same mechanism.

In one study, glycine administration was shown to promote sleep and shorten the time to get into non-REM sleep through mechanisms entirely related to a drop in body temperature resulting from vasodilation of blood vessels.Kawai2015 This cooling down happened about 90 minutes after ingestion.

Vasodilation of blood vessels is necessary so that blood flow to the skin can increase and remove heat from the core. How does this happen—and where? The main site of glycine’s action of vasodilation turned out to be NMDA receptors located in the suprachiasmatic nucleus (SCN)—the part of the brain that regulates circadian rhythms.

Dreamland: Glycine and REM Sleep

Rapid eye movement (REM) sleep is the stage where we dream.

REM sleep also serves other necessary functions: stimulating areas in the brain essential for making and retaining memories, cementing neural connections, and promoting rest and well-being. It’s vital that sleep includes REM (and non-REM) sleep stages and that we spend adequate time in each one.

Important in REM sleep is the process of atonia, where our body becomes temporarily paralyzed so that we don’t act out our dreams. This has probably saved the glass of water on your bedside table from spilling, or your sleeping partner from a swift kick in the shins. When this process fails (termed REM sleep behavior disorder), individuals move, kick, flail about, yell, and even cry out during REM sleep. Simply put—you want your body to be temporarily immobile while you dream.

Glycine has been shown to be responsible for the inhibition of somatic motor neurons during REM sleep that cause a loss of muscle tone.Chase2008 This means it could have a major therapy potential in REM sleep disorders. You can thank glycine that you didn’t kick your significant other out of bed last night—and maybe blame it if you did.

Circadian Rhythms

Circadian rhythms are the master clocks synchronizing what happens inside our body with what is occurring (supposedly) outside of it. When we get hungry, when we get sleepy, and when we perform our best depends on proper function of circadian rhythms. When rhythms are misaligned, physiology gets messy and disease can occur. In fact, desynchronized circadian rhythms have been recently linked to a greater risk for obesity,Broussard2016 cancer, cardiovascular disease,Morris2012 and psychiatric disorders like depression.Baron2014

Studies have shown that administering glycine at certain times of the day could reset a misaligned circadian rhythm, synchronizing the body back to normal.Mordel2011 The suprachiasmatic nucleus (SCN)—a rice-sized region in the brain that controls circadian rhythms—actually contains neurons that are activated by glycine.

Rhythms can fall out of whack due to shift in work schedule, a cross-country trip, even a few late nights on the weekend.

Glycine could possibly be used to realign the body’s internal rhythm and get your physiology back on track.Mordel2011

Melatonin

You may know it better as the “sleep molecule.” Indeed, melatonin production rises throughout the day, peaking at night (in humans) and plays a fundamental role in regulating our circadian rhythms; it controls the entire sleep / wake cycle. This is why so many people take melatonin for sleep issues.

Glycine may indirectly play a role in melatonin production and therefore sleep. This might happen through serotonin. This “feel good hormone” is also known to be involved in the sleep / wake cycle. Serotonin builds up in the brain while we are awake and after enough accumulates, contributes to sleep onset. People with low levels of serotonin tend to spend a lower amount of time in restorative non-REM sleep at night, and also have a higher prevalence of insomnia and depression.Vashadze2007

Where does glycine come in? Glycine ingestion results in an increase in levels of serotonin in the body, and serotonin is used in the synthesis of melatonin.Bannai2011

In sleep disorders that might result from a low amount of melatonin or serotonin in the brain, glycine could augment levels of these sleep-promoting neurotransmitters and help tilt the brain’s balance in favor of rest, relaxation, and happiness.

Rule your own brain chemicals, don't let them rule you.

Supplementation and Sleep

With such a major role in sleep-related processes, there is no surprise that several studies have shown glycine administration before bed can enhance many aspects of sleep and perhaps, even result in other benefits while you’re awake.

All About That Quality

As much as we stress the importance of 7 - 9 hours, the quality of sleep time is just as important. High quality sleep refreshes the brain, solidifies memories, and restores the body and mind. People who report sleep problems have lower working memory and problem-solving speed and increased symptoms of depression.Nebes2009

Glycine improves the quality of sleep. Taken before bed, a dose of 3g glycine stabilized sleep, lowered the time taken to get to sleep (known as sleep onset latency) and reduced the time taken to enter slow-wave sleep (SWS) in poor sleepers.Bannai2012,Inagawa2006 These changes were confirmed using the gold-standard measure of sleep quality, polysomnography (PSG), which measures brain wave activity.

People also report feeling like they slept better after a glycine-induced rest.

A large dose of 3g of glycine was shown to improve participant’s satisfaction with sleep.Yamadera2007 People who received glycine before bed time also reported feeling reduced daytime sleepiness, more feelings of “liveliness and peppiness” during the day and an overall quality of “clear-headedness.”Inagawa2006

This is the type of rest you might expect from a night of sleep after taking certain sleep-aiding supplements as people who use them report feeling more refreshed after waking up, and you could too. These results are in stark contrast to reports following a medication-induced slumber, when daytime performance and mood often suffer the next day, ironically.

Better Sleep Under Stress

Sometimes, our environment or travel schedule just might not allow us the opportunity to get the quality sleep we need. What options are there if you’re already deprived of sleep? Glycine might be a hero here too.

One study gave three grams of glycine to humans who were sleep-restricted to 25% less than their normal sleep for three nights. They had lower levels of fatigue and sleepiness throughout the day and experienced improvements in psychomotor performance compared to a placebo group who didn’t get the supplement.BannaiM2012 After getting only 5.5 hours of sleep for three nights, participants maintained neurobehavioral function and alertness.

Do you have trouble sleeping in hotels or at your in-law’s house? If you’re in an unfamiliar location or situation where a lack of comfort may lead to sleep disturbances, supplementing with glycine could prevent a night of insomnia. Rats who were placed in a new cage environment slept considerably worse—they experienced more sleep disturbances and greater amounts of wakefulness compared with their cozy “home” cage. When these riled rodents received a dose of glycine, wakefulness decreased, non-REM sleep increased, their core body temperature decreased, and brain theta wave activity was enhanced.Kawai2015

Whether you want to go to sleep, sleep deeper, or wake up feeling more refreshed, glycine should definitely be an addition to your sleep-hygiene strategy.

Dosing Glycine for Sleep

Trying to decide how much glycine you need to get the above benefits? The studies done in humans have usually used three grams of glycine. This was typically provided around 1 - 2 hours before bed.

While glycine can be found in capsule form and bought over the counter, it may provide additional benefits when paired with other nootropic ingredients.

Non-habit forming sleep aid nootropics tend to contain ~500mg of L-glycine and are paired with magnesium glycinate, L-theanine, and melatonin; ingredients which have been shown separately to reduce the time to fall asleep, increase sleep quality and efficiency, and reduce stress, anxiety, and inflammation.Brzezinski2005,Unno2013,Nielsen2010

You can take Yawn, along with a glass of water or a small snack, about one hour before sleep (or when you’d like to fall asleep).

Side Effects?

Not really.

When taken at the correct dose, there seem to be little to no adverse effects of glycine treatment. One study has even shown a dose of 5g given three times per day (with a meal) to be well-tolerated.Hippolyte2014 When side effects are reported, common ones include mild abdominal pain, GI issues, or soft stool.

Concerned with glycine making you tired at the wrong time? Even when given at a dose of 9g during the day, it was shown that glycine didn’t promote any unwanted sleepiness.Bannai2012 So, if you’re worried about nodding off during your meeting, no need to worry; glycine can be “non-drowsy.”

Dream On

Maybe you have sleep issues. Maybe you're just trying to improve sleep quality. Maybe you're looking for that extra liveliness during the day to perform and feel better.

Whatever the goal, a good night of sleep can perhaps be attained with a glycine supplement and a soft pillow. You’ve got nothing to lose...other than needing that extra cup of coffee.



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