Melatonin or Glycine: what is the difference

Melatonin and glycine are often mentioned together as «gentle sleep aids», but by nature these are completely different substances. Melatonin is a hormone that tells the body that night has come. Glycine is an amino acid that works as an inhibitory neurotransmitter and affects thermoregulation. The editorial team breaks down how their mechanisms, study data and limitations differ.

What melatonin is

Melatonin is synthesized mainly in the pineal gland from the amino acid tryptophan via serotonin. Its production is controlled by the suprachiasmatic nucleus of the hypothalamus — the «central clock» of the body, which orients itself by the light reaching the retina.

During the day melatonin secretion is minimal, in the evening with the onset of darkness it rises, and the maximum falls in the second half of the night. Bright light, in particular from screens, suppresses this process and shifts the time of the hormone's rise.

Melatonin acts through MT1 and MT2 receptors. The former are associated with reducing the activity of «wakefulness» neurons, the latter with shifting the phase of the circadian rhythm. That is why melatonin is called a chronobiotic: it does not so much «put you to sleep» as adjust the internal clock.

Supplements use synthetic melatonin, identical to the natural one. It is quickly absorbed and has a short half-life — about an hour, so the ordinary form acts briefly, and to maintain sleep through the night a prolonged-release form has been developed.

What glycine is

Glycine is the simplest amino acid, which the body synthesizes on its own and obtains from food, primarily from collagen-rich products: gelatin, broths, poultry skin. It is part of collagen, glutathione and creatine.

In the central nervous system glycine plays a dual role. In the spinal cord and brainstem it is the main inhibitory mediator, acting through glycine receptors. In the brain it is also a co-agonist of NMDA receptors, that is, a necessary participant in excitatory glutamate transmission.

Regarding sleep, another mechanism turned out to be the most interesting. The experiments of Kawai et al. (2015) showed that glycine, through NMDA receptors in the suprachiasmatic nucleus, causes dilation of peripheral vessels and a decrease in internal body temperature — a physiological signal to fall asleep.

Thus, glycine is not a hormone and does not shift the circadian rhythm the way melatonin does. Its possible effect is easing the transition to sleep and improving the subjective quality of sleep.

Comparison of mechanisms and doses

The difference between the substances is already evident in the doses. Studies of melatonin for sleep used from fractions of a milligram to a few milligrams. For glycine in Japanese sleep studies 3 g was used before bed — thousands of times more by mass.

Attention should be paid to the sublingual glycine tablets of 100 mg that are common in Ukraine. Their amount of glycine is much smaller than that studied in the sleep studies, so transferring the results of those studies to such tablets is incorrect.

Thus, melatonin is a tool for managing the timing of sleep, and glycine a potential means for gently improving its quality. These roles overlap only partly.

What the studies show

The meta-analysis by Ferracioli-Oda et al. (2013) on primary sleep disorders showed that melatonin shortens the time to fall asleep and slightly increases total sleep duration. The effect is statistically significant, but modest in absolute magnitude — it is a matter of minutes, not hours.

The most convincing data for melatonin concerns jet lag: the Cochrane review by Herxheimer and Petrie (2002) concluded that melatonin reduces symptoms when crossing several time zones, especially on eastward flights.

For glycine the evidence base is smaller. Inagawa et al. (2006) and Yamadera et al. (2007) reported an improvement in subjective sleep quality and changes on polysomnography after taking 3 g of glycine. Bannai et al. (2012) showed a reduction in daytime fatigue during partial sleep deprivation.

At the same time, the glycine studies were small and were conducted mainly by one group of Japanese scientists. Confident conclusions require independent randomized studies on a larger scale.

Safety and limitations

Melatonin in short-term use is usually well tolerated. The most common side effects are morning drowsiness, headache, dizziness, vivid dreams. It should not be combined with alcohol, and driving after taking it requires caution.

Melatonin can interact with anticoagulants, immunosuppressants, some antidepressants (in particular fluvoxamine, which sharply raises its level) and diabetes medications. For pregnant women and children it is not recommended without a doctor.

• The quality of melatonin supplements is unstable: the analysis by Erland and Saxena (2017) found significant deviations of content from what was stated on the label.
• Glycine in research doses was well tolerated; rarely stomach discomfort is possible.
• People taking clozapine should discuss glycine with a doctor.
• Neither substance treats chronic insomnia on its own.

Glycine is generally considered safe, but there is little data on prolonged intake in large doses. As with melatonin, in the case of prolonged sleep disturbances one should look for the cause rather than merely selecting a supplement.

Editorial conclusions

Melatonin and glycine differ in nature and mechanism: a chronobiotic hormone versus an amino acid that affects inhibition and body temperature.

Melatonin is better studied and has clear indications — primarily circadian rhythm disturbances and jet lag. Glycine has encouraging but limited data on subjective sleep quality.

The doses differ substantially, and small sublingual glycine tablets do not correspond to the amounts studied in the sleep studies.

We also recommend reading our articles on melatonin and magnesium, on 5-HTP and melatonin and on sleep hygiene for athletes.

References

1. Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013;8(5):e63773.
2. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev. 2002;(2):CD001520.
3. Inagawa K, Hiraoka T, Kohda T, Yamadera W, Takahashi M. Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep Biol Rhythms. 2006;4(1):75–77.
4. Yamadera W, Inagawa K, Chiba S, et al. Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep Biol Rhythms. 2007;5(2):126–131.
5. Bannai M, Kawai N, Ono K, Nakahara K, Murakami N. The effects of glycine on subjective daytime performance in partially sleep-restricted healthy volunteers. Front Neurol. 2012;3:61.
6. Kawai N, Sakai N, Okuro M, et al. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology. 2015;40(6):1405–1416.
7. Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275–281.