Sleep deprivation is correlated with a plethora of health conditions such as obesity [1], diabetes[2], and depression[3]. To expand on my last article in the sleep series, I hope to offer some cost effective supplement recommendations to aid in decreasing sleep onset time, reduce the amount of times one wakes during the night and and decrease feelings of fatigue upon waking.

This is for educational purposes only. Consult with you physician before altering your medication and/or supplementation regiments. This article does contain affiliate links for the supplements listed.

L Theanine

My primary resource for this section is a review titled “In Search of a Natural Sleep Aid” from the Journal of the American College of Nutrition. It can be read for free here.

L theanine is an amino acid found in green tea, specifically camellia sinensis [4]. It’s unlike other sleep remedies in that it doesn’t decrease sleep onset or cause drowsiness, while still increasing overall sleep quality. A Japanese study demonstrated this with the experimental group not falling asleep faster than the control, but having lower instances of intermittent awakening and increased feelings of refreshment upon awakening [5]. It’s effects can be best described as anxyolitic and are brought about through a couple different mechanisms. It’s been shown to increase GABA in the brains of mice[6], as well as slightly antagonize glutamate receptors [7]. It is orally bioavailable [8] and can cross the blood brain membrane[9]. 

Key Points:

• L theanine is bioavailable after oral consumption[8], and crosses the blood brain membrane[9].
• L theanine puts you in a parasympathetic state, conducive to sleep, without drowsiness[6][7].
• L theanine supplementation leads to less time awake after falling asleep[5].

The L-Theanine I Use: https://amzn.to/3ObsiFV

Melatonin

Melatonin is a hormone that’s made from serotonin primarily in the pineal gland and then released into the blood[10][11]. Although, it is produced in much smaller amounts in other parts of the brain, at least in mice [12]. It primary function is maintaining circadian rhythm[13]. Melatonin release is regulated by a small part of the brain called the SCN[14] which receives information from neurons in the eyes.
It’s release lowers core body temperature  in preparation for sleep [15] and has inhibitory effects such as lowering dopamine release [10]. Taking melatonin as a  supplement has been shown to decrease sleep onset latency and raise sleep efficiency in regular sleepers. It was also shown to reduce sleep onset in those with a primary sleep condition, an example being insomnia [16]. 
A common fear with regular melatonin supplementation is that it can supposedly lower natural production, leading to dependance. This is not to fear. A 2011 study showed both no tolerance to melatonin or decrease in its natural production in patients supplementing it for both six month and a full year [17].  Melatonin’s production is known to decrease with age, though, as with many other hormones. This in conjunction with its neuroprotective effects, by working as an anti-oxidant, leads to me believe it is worth considering as apart of an HRT protocol in later life.

Key Points:

• Melatonin is a natural produced hormone[10].
• Melatonin supplementation decreases sleep onset in regular sleepers as well as those with insomnia[16].
• Supplementing with melatonin does not decrease natural production[17].
• It can potentially be valuable in an hrt stack due to it’s neuroprotective effects.

The Melatonin I Use: https://amzn.to/43L51QQ

Magnesium

While magnesium doesn’t directly impact sleep, it is still a vital mineral and electrolyte. And over two thirds people in western countries don’t get enough dietary magnesium[19]. 
Besides a playing a role in bone formation[20] it plays a vital role in muscle function and can be used to aid in general relaxation. Calcium causes the fibers in muscles, actomyosin, to bind together and contract. Magnesium counteracts this[21] and moves calcium back into the sarcoplasmic reticulum, allowing muscles to relax. It also has a similar calcium inhibiting effect in the presynaptic cleft that inhibits the release of acetylcholine [22], the neurotransmitter responsible for muscle contraction. Furthermore it magnesium can reduce glutamate signaling, one of the primary excitatory neurotransmitters, specifically at the NMDA receptor.
Overall, magnesium is an often deficient mineral important for muscle relaxation. For these reasons I think it’s a great inclusion in a nightly stack

Key Points:

• 2/3rds of those in the western world are deficient in magnesium[29].
• It plays a key role in muscle relaxation[21][22].

The Magnesium I Use: https://amzn.to/43L51QQ

Sources:

Intro

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082964/

[2] https://pubmed.ncbi.nlm.nih.gov/16983057/

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318605/

L theanine

[4]Lopes Sakamoto F, Metzker Pereira Ribeiro R, Amador Bueno A, Oliveira Santos H. Psychotropic effects of L-theanine and its clinical properties: From the management of anxiety and stress to a potential use in schizophrenia. Pharmacol Res. 2019 Sep;147:104395. doi: 10.1016/j.phrs.2019.104395. Epub 2019 Aug 11. PMID: 31412272. Url:https://pubmed.ncbi.nlm.nih.gov/31412272/

[5] Ozeki M, Juneja LR, Shirakawa S: The effects of theanine on sleep with the actigraph as physiological indicator. Japanese Journal of Physiological Anthropology 9: 13–29, 2004 (in Japanese).

[6] Kimura R, Murata T. Influence of alkylamides of glutamic acid and related compounds on the central nervous system. I. Central depressant effect of theanine. Chem Pharm Bull (Tokyo). 1971 Jun;19(6):1257-61. doi: 10.1248/cpb.19.1257. PMID: 4397636. Url:https://pubmed.ncbi.nlm.nih.gov/4397636/

[7] Kakuda T, Nozawa A, Sugimoto A, Niino H. Inhibition by theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem. 2002 Dec;66(12):2683-6. doi: 10.1271/bbb.66.2683. PMID: 12596867. Url: https://pubmed.ncbi.nlm.nih.gov/12596867/

[8] Kitaoka S, Hayashi H, Yokogoshi H, Suzuki Y. Transmural potential changes associated with the in vitro absorption of theanine in the guinea pig intestine. Biosci Biotechnol Biochem. 1996 Nov;60(11):1768-71. doi: 10.1271/bbb.60.1768. PMID: 8987851. Url:https://pubmed.ncbi.nlm.nih.gov/8987851/

[9] Terashima T, Takido J, Yokogoshi H. Time-dependent changes of amino acids in the serum, liver, brain and urine of rats administered with theanine. Biosci Biotechnol Biochem. 1999 Apr;63(4):615-8. doi: 10.1271/bbb.63.615. PMID: 10361674. Url:https://pubmed.ncbi.nlm.nih.gov/10361674/

Melatonin

[10]  Url:https://www.eajm.org/en/a-review-of-melatonin-its-receptors-and-drugs-161770

[11 ] http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/pineal.html

[12] Liu YJ, Zhuang J, Zhu HY, Shen YX, Tan ZL, Zhou JN. Cultured rat cortical astrocytes synthesize melatonin: absence of a diurnal rhythm. J Pineal Res. 2007 Oct;43(3):232-8. doi: 10.1111/j.1600-079X.2007.00466.x. PMID: 17803519. Url:https://pubmed.ncbi.nlm.nih.gov/17803519/

[13] Masters A, Pandi-Perumal SR, Seixas A, Girardin JL, McFarlane SI. Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment. Brain Disord Ther. 2014;4(1):1000151. doi: 10.4172/2168-975X.1000151. PMID: 25705578; PMCID: PMC4334454. Url:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334454/

[14] Doghramji K. Melatonin and its receptors: a new class of sleep-promoting agents. J Clin Sleep Med. 2007 Aug 15;3(5 Suppl):S17-23. PMID: 17824497; PMCID: PMC1978320. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1978320/

[15] REID, K., VAN DEN HEUVEL, C. and DAWSON, D. (1996), Day-time melatonin administration: Effects on core temperature and sleep onset latency. Journal of Sleep Research, 5: 150-154. https://doi.org/10.1046/j.1365-2869.1996.t01-1-00006.xUrl:https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1365-2869.1996.t01-1-00006.x

[16] Buscemi N, Vandermeer B, Pandya R, et al. Melatonin for Treatment of Sleep Disorders: Summary. 2004 Nov. In: AHRQ Evidence Report Summaries. Rockville (MD): Agency for Healthcare Research and Quality (US); 1998-2005. 108. Url:https://www.ncbi.nlm.nih.gov/books/NBK11941/

[17] Lemoine P, Garfinkel D, Laudon M, Nir T, Zisapel N. Prolonged-release melatonin for insomnia – an open-label long-term study of efficacy, safety, and withdrawal. Ther Clin Risk Manag. 2011;7:301-11. doi: 10.2147/TCRM.S23036. Epub 2011 Jul 26. PMID: 21845053; PMCID: PMC3150476. URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3150476

[18] Anghel L, Baroiu L, Popazu CR, Pătraș D, Fotea S, Nechifor A, Ciubara A, Nechita L, Mușat CL, Stefanopol IA, Tatu AL, Ciubara AB. Benefits and adverse events of melatonin use in the elderly (Review). Exp Ther Med. 2022 Mar;23(3):219. doi: 10.3892/etm.2022.11142. Epub 2022 Jan 14. PMID: 35126722; PMCID: PMC8796282. Url:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8796282/

[19]  Url: https://pubmed.ncbi.nlm.nih.gov/29093983/

Magnesium

[20] Rondanelli M, Faliva MA, Tartara A, Gasparri C, Perna S, Infantino V, Riva A, Petrangolini G, Peroni G. An update on magnesium and bone health. Biometals. 2021 Aug;34(4):715-736. doi: 10.1007/s10534-021-00305-0. Epub 2021 May 6. PMID: 33959846; PMCID: PMC8313472. Url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313472/

[21]Biochemistry 1969, 8, 6, 2266–2271 Publication Date:June 1, 1969 https://doi.org/10.1021/bi00834a005

[22] DEL CASTILLO J, ENGBAEK L. The nature of the neuromuscular block produced by magnesium. J Physiol. 1954 May 28;124(2):370-84. doi: 10.1113/jphysiol.1954.sp005114. PMID: 13175138; PMCID: PMC1366273. Url:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1366273/