Glycine, Sleep, And Muscle

Glycine structure

Glycine Improves Sleep And Increases Muscle Mass

Glycine is an amino acid that makes up a large part of gelatin/collagen. Amino acids are generally categorized as essential or non-essential. Essential amino acids are those which cannot be made from other materials within the body, but which there is a biological requirement for. Glycine can be synthesized but dietary intake and biological requirements have led some researchers to categorise glycine as a semi-essential amino acid(*). In my previous article I looked at the effect of glycine on longevity (*). This article takes a look at some benefits of glycine on sleep quality and muscle mass.

Glycine And Sleep

A number of studies have reported an improvement in sleep quality from 3g glycine before bed. Users report better sleep, and sleep studies show objective improvements. Glycine is also shown to improve performance in people who have not had enough sleep, though perhaps not with consecutive nights of poor sleep.

One study took 19 participants with reported sleep problems and gave them 3 g glycine one hour before bed. The study was a randomised, double-blind, crossover trial using a questionnaire to assess outcomes. 15 of 19 participants finished the study and there were reported improvements in energy and clear headedness the day after glycine supplementation.

“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.”(*)

Another study took 10 volunteers and looked at glycine with regard to restricted sleep. Average sleep time for all the participants was calculated over three nights prior to the experiment. During the experiment the participants sleep time was restricted by 25% of their average. The participants took 3 g of glycine or placebo 30 minutes before bed. The participants again completed questionnaires and this time also completed tests of mental performance, this was repeated for three nights and the three following days. Glycine supplementation led to improvements in fatigue on day one, but by day three there was no benefit on fatigue. Objective tests of performance showed improvements in the glycine group on day one through three.

“Sleep was restricted to 25% less than the usual sleep time for three consecutive nights. Before bedtime, 3 g of glycine or placebo were ingested, sleepiness, and fatigue were evaluated using the visual analog scale (VAS) and a questionnaire, and performance were estimated by personal computer (PC) performance test program on the following day. In subjects given glycine, the VAS data showed a significant reduction in fatigue and a tendency toward reduced sleepiness. These observations were also found via the questionnaire, indicating that glycine improves daytime sleepiness and fatigue induced by acute sleep restriction. PC performance test revealed significant improvement in psychomotor vigilance test.(*)

A follow-up to the first study looked at objective measures of sleep quality. This study introduced polysomnography, the use of multiple electronic devices reporting bio-physiological changes during sleep. This type of monitoring is similar or identical to that used in a “sleep study”. This was a randomised single-blinded, crossover trial with 11 participants who had reported ongoing sleep problems. The study also reported on questionnaires completed by the participants. Those taking glycine reported having significantly increased sleep satisfaction, less difficulty getting to sleep, faster sleep onset and greater sleep duration.

Results of the polysomnographic sleep study supported some of the participants reports. The participants got to sleep quicker and they reached deep sleep quicker. REM and sleep architecture were unchanged, alterations here might indicate a sedative effect, rather than an improvement in “natural sleep”, so this was a big plus. A questionnaire assessing sleepiness and energy the next day showed that the participants felt slightly less fatigue after having taken glycine the night before. Glycine seems to improve sleep quality without the side effects associated with many other “solutions”.

“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.”(*)

Glycine And Muscle

There are relationships between sleep (particularly slow wave or deep sleep), hormones, and muscle mass. Glycine also has anabolic and anti-catabolic effects which could lead to increased lean body mass, though most of these discoveries are in animals or cell studies. A 2014 study looking at pig intestinal epithelial cells showed a massive increase in protein synthesis with glycine. In some examples from this study glycine increased cell growth by over 200%, increased protein synthesis by over 400%, and decreased protein degradation by up to 28%.

“Compared with 0.0–0.5 mmol/L glycine, 1.0 mmol/L glycine enhanced (P < 0.05) cell growth (by 8–24% on day 2 and by 34–224% on day 4, respectively) and protein synthesis (by 36–419%) while reducing (P < 0.05) protein degradation (by 7–28%). This effect of glycine was associated with activation of the mammalian target of rapamycin signaling pathway in enterocytes.”(*)

Another experiment (in mouse myoblast cells) showed similar effects. Glycine increased protein synthesis by 20% to 80% and decreased protein metabolism by up to 30%. This study also shows that glycine enhances mTORC1, a controller of protein synthesis also enhanced by resistance training.

“Compared with control cells, 0.25–1.0 mmol glycine/L enhanced cell growth (by 12–15%) after 24 h (P < 0.05). Glycine treatment led to increased DNA replication (by 70–80%) while enhancing mTORC1 activation by upregulating Akt and inhibiting AMPK signaling (P < 0.05). Accordingly, glycine exposure increased (P < 0.05) the rate of protein synthesis (by 20–80%) and inhibited (P < 0.05) the rate of protein degradation (by 15–30%) in a concentration-dependent manner in C2C12 cells…
These findings indicate that glycine plays a previously unrecognized role in enhancing protein synthesis and inhibiting protein degradation in C2C12 cells. Glycine regulates protein turnover by activating mTORC1 and by inhibiting the expression of genes for proteolysis. Our results indicate that glycine is a functional amino acid that improves muscle cell growth.”(*)

Another study conducted in 2014 looked at glycine supplementation in two week old piglets. The article proposed that low levels of glycine in milk may limit the growth of animals. 60 piglets were divided into four groups of 15. They were supplemented with different increments of glycine in the diet – 0%, 0.5%, 1.0%, and 2.0% of total calories. The animals all received the same amount of food (milk). Bodyweight increased with glycine supplementation, but body composition was not affected, the animals were larger but not fatter. They weren’t leaner either, animals fed 2% glycine were approximately 14% heavier than those without glycine supplementation, body fat percentage was 12.4% in the 0% glycine group and 12.3% in the 2% glycine group.

“Compared with control piglets, dietary supplementation with 0.5, 1 and 2 % glycine increased (P < 0.05) plasma concentrations of glycine and serine, daily weight gain, and body weight without affecting body composition, while reducing plasma concentrations of ammonia, urea, and glutamine, in a dose-dependent manner…
The findings not only enhance understanding of protein nutrition, but also have important implications for designing improved formulas to feed human infants, particularly low birth weight and preterm infants.(*)

The anti-inflammatory effects of glycine are pretty well understood and this was the reason for a study into the effects of glycine on muscle wasting in cancer. This experiment induced cancer in mice and then administered glycine by subcutaneous injection for three weeks. Glycine blunted the increase in inflammatory markers and slowed the loss of body mass and skeletal muscle.

Glycine attenuated the loss of fat and muscle mass, blunted increases in markers of inflammation (F4/80, P = 0.01 & IL-6 mRNA, P = 0.01) and atrophic signaling (MuRF, P = 0.047; atrogin-1, P = 0.04; LC3B, P = 0.06 and; BNIP3, P = 0.10) and tended to attenuate the loss of body mass (P = 0.07), muscle function (P = 0.06), and oxidative stress (GSSG/GSH, P = 0.06 and DHE, P = 0.07) seen in tumor-bearing mice. Preliminary studies that compared the effect of glycine administration with isonitrogenous doses of alanine or citrulline showed that the observed protective effect was specific to glycine.
Glycine protects skeletal muscle from cancer-induced wasting and loss of function, reduces the oxidative and inflammatory burden, and reduces the expression of genes associated with muscle protein breakdown in cancer cachexia. Importantly, these effects were glycine specific.(*)

A 2009 study lends some support to the idea that glycine could increase or protect muscle mass in humans. This study compared the effect of whey protein vs collagen hydrolysate on nitrogen retention. Collagen has a relatively high amount of glycine. The study showed increased nitrogen excretion during the whey supplementation arm of the trial, indicating that glycine-rich collagen protects muscle mass relative to whey. That said, glycine and collagen are entirely not interchangeable. 

“Nine healthy elderly women (age 71±1 years) were provided a eucaloric diet containing approximately the protein Recommended Dietary Allowance of 0.8 g/kg body weight/day….
Body weight decreased (P=0.02) after consumption of the whey supplement, with no significant changes in body weight or composition resulting from the consumption of the collagen supplement. Nitrogen excretion was higher during the whey supplement trial than during the collagen trial (P=0.047). Therefore, a concentrated, fortified, hydrolyzed collagen protein supplement maintained nitrogen balance and preserved lean body mass during 15 days of consumption of a relatively low-protein diet.”(*)

Glycine may suppress muscle breakdown by lowering stress hormones.

“The plasma corticosterone concentration was also decreased by glycine, but the plasma insulin concentration was unaffected. These results indicate that orally administered glycine suppresses myofibrillar proteolysis and expression of proteolytic-related genes of skeletal muscle by decreasing the plasma corticosterone concentration in chicks.”

It can also prevent muscle wasting from endotoxin/LPS (often via leaky gut), there are many studies showing benefits from glycine in the GI tract.

“However, the normal anabolic response to amino acids is impaired during musclewasting conditions…
The nonessential amino acid glycine has anti-inflammatory and antioxidant properties and preserves muscle mass in calorie-restricted and tumor-bearing mice. We hypothesized that glycine would restore the normal muscle anabolic response to amino acids under inflammatory conditions…
 Whereas leucine failed to stimulate muscle protein synthesis in LPS-treated mice pretreated with l-alanine (isonitrogenous control), leucine robustly stimulated protein synthesis (+51%) in mice pretreated with 1 g/kg glycine
Our observations in male C57BL/6 mice suggest that glycine may represent a promising nutritional intervention for the attenuation of skeletal muscle wasting.(*)

Glycine can prevent muscle loss in caloric restriction, it also accelerates fat loss when dieting.

Eight weeks of a high-fat diet (HFD) induced obesity and glucose intolerance. CR caused rapid weight loss (ALA: 20%, GLY: 21%, P < 0.01), reduced whole-body fat mass (ALA: 41%, GLY: 49% P < 0.01), and restored glucose tolerance to control values in ALA and GLY groups. GLY treated mice lost more whole-body fat mass (14%, p < 0.05) and epididymal fat mass (26%, P < 0.05), less lean mass (27%, P < 0.05), and had better preserved quadriceps muscle mass (4%, P < 0.01) than ALA treated mice after 20 d CR. Compared to the HFD group, pro-inflammatory genes were lower (P < 0.05), metabolic genes higher (P < 0.05) and S6 protein phosphorylation lower after CR, but not different between ALA and GLY groups. There were significant correlations between %initial fat mass (pre CR) and the mRNA expression of genes involved in inflammation (r = 0.51 to 0.68, P < 0.05), protein breakdown (r = −0.66 to −0.37, P < 0.05) and metabolism (r = −0.59 to −0.47, P < 0.05) after CR…
Taken together, these findings suggest that glycine supplementation during CR may be beneficial for preserving muscle mass and stimulating loss of adipose tissue.(*)

Most people are not getting adequate glycine. A 2009 paper from The Journal of Biosciences argues that dietary glycine, plus what we can synthesize from other amino acids, comes far short of our requirements for just collagen production, glycine is essential for other things, not least glutathione production.. They estimate most people get/make 4.5 to 6g per day total, with a minimum requirement of 10g for collagen synthesis in a 70kg individual ((*)). In the past humans likely ate a lot more glycine in the form of gelatinous parts of animals. Gelatin is about 25% glycine. Current diets are more skewed toward methionine rich and glycine poor meats. Just how much glycine is good or optimal isn’t clear, but a study using .8g/kg, or 56g of glycine per day in a 70kg individual, was well tolerated. The study showed a significant reduction in schizophrenia metrics (11). I take about 15/20g free glycine per day. I haven’t noticed much any difference in different brands of glycine, unlike most supplements.  Bulksupplements Glycine Powder looks good in the US. I’ve also started using great lakes collagen as there are some benefits to this above what is had with free glycine. If you can get large amounts of collagen from the diet that might be your best strategy.