[Pressure] Tired of feeling tired but more tired

[UARSBAL]

Hi,
 
I’ve been having daytime somnolence and unrefreshed sleep my whole life (now 45 years of age, 65kg, 5,5”, male) and had a sleep study 10 years ago which was negative, but things have certainly got worse.  I visited a dentist for Bruxism/jaw pain who identified I may have sleep apnea and made a referral for a complete diagnosis.  The private ENT specialist I saw recommends a CPAP should be trialed due to the flexible nasendoscopy showing very narrow circumferential pharyngeal constrictor muscles which unfortunately are not amenable to any surgical and made a diagnosis of possible UARs.
 
My UK Private Insurance won’t cover the sleep study or CPAP machines and currently awaiting an appointment on the NHS. 
 
Meanwhile, I have learned about UARs and bought the AirSense 10 Auto CPAP machine and F&P Evora Full-face mask and have been using it for circa a month, here are the results from Oscar.
 
   
   
   

As I’ve been feeling more tired than before so have been increasing the pressure from 4 to 10 but am still feeling more tired than before and wondering if I need to persevere or try some other settings.
 
Many thanks.
Bal

[BoxcarPete]

I don't see any major red flags in your chart, things appear to be going fairly well from a sleep standpoint. What else have you looked into, specifically blood work for thyroid, testosterone, vitamin D, etc?

[PeaceLoveAndPizza]

Please report the chart replacing tidal volume with respiration rate.

[UARSBAL]

I don't see any major red flags in your chart, things appear to be going fairly well from a sleep standpoint. What else have you looked into, specifically blood work for thyroid, testosterone, vitamin D, etc?

I had a blood test for D, thyroid, liver, etc and it all appeared within range.  I don't think it included a testosterone test so am trialing testosterone supplements. 

Is posting blood results permitted?

---

Please report the chart replacing tidal volume with respiration rate.

Hi, 

The respiration rate is in the other attached image.  Hope that helps.

Thanks.

[PeaceLoveAndPizza]

I actually was hoping to see flow rate and respiration rate on a single chart so I don’t have to keep flipping screens, but I shall make this work.

Without a sleep study it is difficult to make a call of UARS, but the chart posted does show arousals. Whether they are UARS or not will need more study.

Overall things look decent, but when you look closely there are arousals that can be seen in both the flow rate and respiration rate graphs. Those “gasps” are likely sufficient to bring you out of a deeper state of sleep, or keep you from getting there in some cases. Your flow limitations are being managed, so that is good.

The cluster of CA’s around 00:10 given the rapidity of the events leads me to think that was a chin-tuck or possibly you rolled onto your back. The tidal volume in the same time frame is showing big, deep breaths, so you likely were  not fully asleep. The CA’s at the end are likely from coming out of a deeper sleep and should resolve as you adjust to the machine and settings.

For now, I think staying with the current settings a while longer before bumping up pressure a wee bit, maybe in 0.2 increments, should help. There is a point where the pressure should help with the arousals, but cross that point and it will create other issues. It is a fine-line many of us have to balance.

One other observation is the I:E ratio (inspiration to expiration). Yours are close to 1:1, which in many cases leads to thinking there are still unresolved flow limitations. A soft cervical collar and/or flatter CPAP friendly pillow that will help keep your airway open may be worth the few quid they will cost. If you do a 2-3 minute zoom in around 02:00 or 04:25 you will likely see flat-top or angled waveforms at the peak indicative of flow limitations. It is not too bad as it is not registering more, but still something to try to smooth out for a better sleep.

[quietlyamuck]

I had a blood test for D, thyroid, liver, etc and it all appeared within range.  I don't think it included a testosterone test so am trialing testosterone supplements. 

It is likely that none of the “tests” were full diagnostic panels.  Even getting the basic 25-OH-cholecalciferol level (one form of and one step in the pathway that results in the synthesis of active vitamin D in the kidney; the result of the conversion of pre vitamin D through sun exposure) is, even now, relatively rare.  The thyroid test included in the panel was a TSH.  This is important because TSH is a hormone produced by the pituitary in response to feedback from the thyroid but, by itself, it is surveillance rather than reconnaissance.  In terms of testosterone, a serum testosterone taken after 9 am is good enough to guesstimate if a sufficient amount is being produced, had a reduced level been found, two levels from separate blood draws before 9 am would be necessary for diagnostic purposes.  However, testosterone is found in the blood bound to a variety of things, one of these, sex hormone binding globulin appears to increase with age, since that testosterone is not immediately available, it is possible to experience all manner of symptoms even with what might otherwise appear to be a normal serum level.  Other than testosterone (and HCG or kisspeptin-10) there is no supplement that will increase the production of testosterone for a given blood level of LH without a clinically significant deficiency (that is, you would experience notable symptoms of the mineral deficiency in its own right before you'd notice any symptoms of a testosterone deficiency) of something.  (Continued)

[quietlyamuck]

I was having some sort of problem with the connection to the forum because I would type and the letters would not appear for a second or two; it was as if I was typing back in 1984!

I have some knowledge in this area and I can tell you that no supplement currently sold will increase the amount of testosterone produced for a given blood level of LH. You may well have a deficiency of testosterone, I do not know; nevertheless, unless you are markedly undernourished, no supplement will result in a statistically significant increase in testosterone production over the medium to long term; in the short term, due to temporary reductions in SHBG, a small increase in free testosterone has been seen on occasion. Having said that, the western diet has been shown to be deficient in magnesium and potassium. The standard test will show a blood level of a mineral, to actually look at what your body has available as stored (mineral) you need an ionized (mineral) test. Having said that, unless you have one of several very serious kidney conditions, a modest chelate supplement will be as harmless as a potato skin and considerably easier to consume. There is some work that was done in Japan regarding the consumption of a glycine supplement (the amount that is effective varied anywhere from 4 grams to 10 grams and, for some people, the quantity that makes them sick to their stomach —glycine is a very effective anti acid— is less, at least initially, than the amount that will be effective) and the quality and the perception of the quality of sleep. It is also the case that glycine is the basic skeleton on which GABA is made and magnesium is a GABA agonist as well. Avoid the salts but if you are going to get a salt then citrate is the most bioavailable form other than the amino acid chelates. I cannot guarantee that you will sleep for a longer period of time but the materials I have read do suggest that sufficient magnesium is necessary for muscular relaxation and that deficiency states have significant effects. In my own personal experience, sufficient magnesium is the difference between rolling over after a nightmare and sitting up for hours. I have also found the work on glycine to translate to my own personal experience in terms of the quality and the perception. In and of itself, I have not yet found something that increases the length of time that I am asleep but I can and do take the glycine when I wake up and back to sleep I go.

Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review

Meerza Abdul Razak, 1 Pathan Shajahan Begum, 2 Buddolla Viswanath, 3 and Senthilkumar Rajagopal 1 , *
Author information Article notes Copyright and License information PMC Disclaimer
This article has been corrected. See Oxid Med Cell Longev. 2022; 2022: 9857645.
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Abstract
Glycine is most important and simple, nonessential amino acid in humans, animals, and many mammals. Generally, glycine is synthesized from choline, serine, hydroxyproline, and threonine through interorgan metabolism in which kidneys and liver are the primarily involved. Generally in common feeding conditions, glycine is not sufficiently synthesized in humans, animals, and birds. Glycine acts as precursor for several key metabolites of low molecular weight such as creatine, glutathione, haem, purines, and porphyrins. Glycine is very effective in improving the health and supports the growth and well-being of humans and animals. There are overwhelming reports supporting the role of supplementary glycine in prevention of many diseases and disorders including cancer. Dietary supplementation of proper dose of glycine is effectual in treating metabolic disorders in patients with cardiovascular diseases, several inflammatory diseases, obesity, cancers, and diabetes. Glycine also has the property to enhance the quality of sleep and neurological functions. In this review we will focus on the metabolism of glycine in humans and animals and the recent findings and advances about the beneficial effects and protection of glycine in different disease states.

Beneficial Effects of the Amino Acid Glycine

Israel Pérez-Torres, Alejandra María Zuniga-Munoz, Veronica Guarner-Lans 1
Affiliations expand
PMID: 27292783 DOI: 10.2174/1389557516666160609081602
Abstract

Glycine is the smallest non-essential, neutral and metabolically inert amino acid, with a carbon atom bound to two hydrogen atoms, and to an amino and a carboxyl group. This amino acid is an essential substrate for the synthesis of several biologically important biomolecules and compounds. It participates in the synthesis of proteins, of the tripeptide glutathione and in detoxification reactions. It has a broad spectrum of anti-inflammatory, cytoprotective and immunomodulatory properties. To exert its actions, glycine binds to different receptors. The GlyR anion channel is the most studied receptor for glycine. However, there are GlyR-independent mechanisms for glycine cytoprotection and other possible binding molecules of glycine are the NMDA receptor and receptors GlyT1 and GlyT2. Although, in humans, the normal serum level of glycine is approximately 300 μM, increasing glycine intake can lead to blood levels of more than 900 μM that increase its benefic actions without having harmful side effects. The herbal pesticide glyphosate might disrupt glycine homeostasis. Many in vitro studies involving different cell types have demonstrated beneficial effects of the addition of glycine. Glycine also improved conditions of isolated perfused or stored organs. In vivo studies in experimental animals have also tested glycine as a protector molecule and some studies on the beneficial effects of glycine after its clinical application have been done. Although at high-doses, glycine may cause toxic effects, further studies are needed to investigate the safe range of usage of this aminoacid and to test the diverse routes of administration.

Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes
Wataru YAMADERA, Kentaro INAGAWA, Shintaro CHIBA, Makoto BANNAI, Michio TAKAHASHI, Kazuhiko NAKAYAMA
First published: 27 March 2007 https://doi.org/10.1111/j.1479-8425.2007...xCitations: 3
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
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Abstract
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.

Subjective effects of glycine ingestion before bedtime on sleep quality
Kentaro INAGAWA, Takenori HIRAOKA, Tohru KOHDA, Wataru YAMADERA, Michio TAKAHASHI
First published: 09 February 2006 https://doi.org/10.1111/j.1479-8425.2006.00193.x

Abstract
The effects of glycine on sleep quality were examined in a randomized double-blinded cross-over trial. The volunteers, with complaints about the quality of their sleep, ingested either glycine (3 g) or placebo before bedtime, and their subjective feeling in the following morning was evaluated with the St. Mary's Hospital Sleep Questionnaire and Space-Aeromedicine Fatigue Checklist. The 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.

Neuropsychopharmacology. 2015 May; 40(6): 1405–1416.
Published online 2015 Jan 14. Prepublished online 2014 Dec 23. doi: 10.1038/npp.2014.326
PMCID: PMC4397399
PMID: 25533534
The Sleep-Promoting and Hypothermic Effects of Glycine are Mediated by NMDA Receptors in the Suprachiasmatic Nucleus

Nobuhiro Kawai,1,4 Noriaki Sakai,2,4 Masashi Okuro,2,3 Sachie Karakawa,1 Yosuke Tsuneyoshi,1 Noriko Kawasaki,1 Tomoko Takeda,1 Makoto Bannai,1,* and Seiji Nishino2
Author information Article notes Copyright and License information PMC Disclaimer
Associated Data

Supplementary Materials
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Abstract
The use of glycine as a therapeutic option for improving sleep quality is a novel and safe approach. However, despite clinical evidence of its efficacy, the details of its mechanism remain poorly understood. In this study, we investigated the site of action and sleep-promoting mechanisms of glycine in rats. In acute sleep disturbance, oral administration of glycine-induced non-rapid eye movement (REM) sleep and shortened NREM sleep latency with a simultaneous decrease in core temperature. Oral and intracerebroventricular injection of glycine elevated cutaneous blood flow (CBF) at the plantar surface in a dose-dependent manner, resulting in heat loss. Pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists AP5 and CGP78608 but not the glycine receptor antagonist strychnine inhibited the CBF increase caused by glycine injection into the brain. Induction of c-Fos expression was observed in the hypothalamic nuclei, including the medial preoptic area (MPO) and the suprachiasmatic nucleus (SCN) shell after glycine administration. Bilateral microinjection of glycine into the SCN elevated CBF in a dose-dependent manner, whereas no effect was observed when glycine was injected into the MPO and dorsal subparaventricular zone. In addition, microinjection of D-serine into the SCN also increased CBF, whereas these effects were blocked in the presence of L-701324. SCN ablation completely abolished the sleep-promoting and hypothermic effects of glycine. These data suggest that exogenous glycine promotes sleep via peripheral vasodilatation through the activation of NMDA receptors in the SCN shell.

Note that polysomnographic changes have been observed and that time efficiency improvements were also observed. I have often wondered if the feeling of being warm that accompanies the awake periods that occur during what I wish was a 10 hour period of continuous sleep are the reason I am waking up rather than the effect of something else, it would appear that there is something to this.

[quietlyamuck]

I posted some references on glycine, rather than references concerning testosterone, because, I believe that in this forum, the material concerning glycine is of greater importance and will be more useful to more people. There is a great deal more work in this area and I do not recall reading anything concerning glycine supplementation and either the initiation or the efficiency of sleep in this forum over the years. Having said that, I will admit that I spent far more time reading the forum when I first began treatment for sleep disordered breathing.

[quietlyamuck]

Peace Love and Pizza: I need to sleep on my back, can I infer from what you are saying that sleeping on my back can, absent an apnea event, produce sufficient arousal from respiratory effort so that I would wake up even with the inflow pressure from the —in my case— BiPAP? Can I also infer from the event related to the chin tuck that sleeping without a pillow would result in a better outcome? This might seem obvious but the bed at every sleep study I have undergone has had, not only one, multiple and thick pillows! You also mentioned a soft c-collar, is that something that can improve the outcome of the treatment in general? As you can see, I have focused on a different approach to improving my sleep but I’d gladly wear a c-collar if that would improve my sleep efficiency?

[UARSBAL]

Thanks for the detailed response information regarding Testosterone and Magnesium, of which I'm taking both supplements
 
I have organised the rows in Oscar with those you've highlighted so will make reading them easier from here on :-)
 
Sadly, I have had to reduce the pressure to 8 as I have been suffering bloating but will gradually increase\decrease in 0.2 increments and persevere for now.  I shall also take a look at the recommendation of CPAP pillow.