GABA and 5-HTP - Expect changes in Sleep Architecture?

In an attempt to get more and deeper sleep, I've just started taking GABA and 5-HTP.

Over the course of the last few days, I've found that my AHI has gone from .6 to 2.0, the durations of my apneas have increased on average from 10 - 12 seconds to about 14 - 20 seconds each. Oddly, however, I'm able to get more mask time - 10 hours instead of 7.5, and I feel a little more rested. I'm curious if anyone is familiar with either of these supplements alone or in combination and whether others have had success or otherwise with either or both.

Well, I'm still taking the standardized passionflower extract to increase GABA as we discussed last month a la Eric Braverman MD's book, The Edge Effect, to heal my prime deficiency. My sleep is more restful with my frequent wakeups reduced dramatically. My AHI is lower overall but that may be because I'm able to sleep part of the night on my side as my shoulder is healing, both the AI and HI components are reduced.

Could be you're sleeping not only longer but deeper. Deeper sleep might mean more REM. More REM might mean more events. What are you seeing on your recording oximeter? How do you feel?

Muse-Inc wrote:Well, I'm still taking the standardized passionflower extract to increase GABA as we discussed last month a la Eric Braverman MD's book, The Edge Effect, to heal my prime deficiency. My sleep is more restful with my frequent wakeups reduced dramatically. My AHI is lower overall but that may be because I'm able to sleep part of the night on my side as my shoulder is healing, both the AI and HI components are reduced.

Could be you're sleeping not only longer but deeper. Deeper sleep might mean more REM. More REM might mean more events. What are you seeing on your recording oximeter? How do you feel?

The oximeter shows deeper desats, but the durations are still just short blips. I feel better, I think. I'm going to continue with the oximetry for a little longer.

I'd forgotten about the passion flower extract. I'm glad to hear your sleep and AHI are both better! Excellent. We'll have a lot to discuss next Saturday.

GABA and 5HTP are natural neuro-chemicals produced in the brain. I would get your doctor's opinion before using either. 5HTP usually refers to seritonin. Seritonin is associated with depression. GABA regulates dopamine production.

DreamDiver, are you sleeping more hours or just wearing your mask more of the time? Do you typically sleep 10 hours a night? That's quite a bit...

SleepingUgly wrote:DreamDiver, are you sleeping more hours or just wearing your mask more of the time? Do you typically sleep 10 hours a night? That's quite a bit...

My normal mask time is 7.5 hours. Ordinarily, I find it difficult to stay in bed any longer than that. I'm much too awake to make it worth my while to stay masked. Normal sleep time is much less than mask time because I turn over pretty much all night long. I have no way to measure this. Every time I turn over, I generally have to rearrange the hose. I turn over perhaps 10 to 15 times a night. Somewhere in there I'm getting light sleep and dreaming. I'm not getting enough restorative sleep because I know I wake too often to actually cycle through a reasonable, normal sleep pattern. If I stay in one position too long, I either get numb, feel pain in my extremities or just plain can't breathe. This is a sleep arousal thing that doesn't seem to be addressed by the CPAP, and seems almost certainly to be out of the purvue of the doc-in-box style sleep medicine that BCBS PPO insurance will pay for in Georgia. I've done everything I can do to address my CPAP usage: leaks, AHI, pressure, etc. Now I'm trying to find ways to force my body to accept a pattern of deeper sleep using other means because I know the CPAP side of things has been addressed as far as it can go with the machinery and diagnosis I have.

I can get back to sleep easier after turning over when I take these. Hence, I can sleep longer in hopes of getting more actual restorative sleep. I still don't know if that's actually happening though because, again, I can't measure whether I'm getting NR3 sleep.

I don't know if I'm robbing Peter to pay Paul, so to speak: In getting 10 hours of mask time a night, am I making things worse by exposing myself to more and longer AHI? I don't know. I think I feel better, but this could be a hopeful placebo effect. So I'm looking for input.

LarryD wrote:5HTP usually refers to seritonin.

Nope. That'd be 5HT, 5-hydroxytryptamine. 5HTP, 5-hydroxytryptophan, is a precursor to 5HT/serotonin but is not the same thing.

One very important difference is that 5HT does not readily cross the blood-brain barrier, so eating serotonin is just going to cause nausea and diarrhea but won't affect much in the brain. Eating 5HTP can, presumably, increase brain serotonin by crossing the BBB then being converted. It will, of course, also increase serotonin in other areas and that can still lead to side effects.

LarryD wrote:Seritonin is associated with depression.

Serotonin is associated with all sorts of things, including nausea and diarrhea. It all depends on what receptors are being activated. Insufficient serotonin activity in certain brain regions has been associated with depression. The same can be said of norepinephrine and dopamine as well as several other compounds.

LarryD wrote:GABA regulates dopamine production.

GABA's primary function in humans is that it binds to GABA receptors, which are inhibitory. I have never heard of an effect exerted by GABA via regulation of dopamine production.

DreamDiver wrote:In an attempt to get more and deeper sleep, I've just started taking GABA and 5-HTP.

Orally-ingested (or even systemically-injected) GABA does not readily cross the blood-brain barrier, which means it isn't going to be able to bind to the GABA receptors that could affect sleep. The only effective way to add GABA to the brain is to inject it directly into the brain. This is not recommended. We mostly get at GABA receptors by giving drugs that can mimic GABA at receptor sites and that do cross the BBB. There are many examples, including things from Valium to Jack Daniel's. These compounds are fairly famous for decreasing sleep latency but decreasing sleep efficiency and suppressing delta wave sleep - they make you sleepy, but your sleep sucks.

5HTP, like l-tryptophan, is a serotonin precursor that has been shown in some studies to promote sleep. The presumed mechanism is indirect: 5HTP can cross the blood-brain barrier then be converted into serotonin, which then can bind to serotonin receptors. Of course, some of those receptors can make people sleep while others can wind people up. You can't aim either the 5HTP or serotonin itself at any particular receptors, so it's a bit of a crapshoot. Generally speaking, serotonin's effects of increasing nausea (by binding to 5HT3 receptors both in the brain and in the gut) and of increasing diarrhea (by binding to to receptors in the myenteric plexus and promoting peristalsis) outweigh its effects on sleep.

Neither one of these is something that I'd personally be willing to try.

mstevens wrote:

DreamDiver wrote:In an attempt to get more and deeper sleep, I've just started taking GABA and 5-HTP.

Orally-ingested (or even systemically-injected) GABA does not readily cross the blood-brain barrier, which means it isn't going to be able to bind to the GABA receptors that could affect sleep. The only effective way to add GABA to the brain is to inject it directly into the brain. This is not recommended. We mostly get at GABA receptors by giving drugs that can mimic GABA at receptor sites and that do cross the BBB. There are many examples, including things from Valium to Jack Daniel's. These compounds are fairly famous for decreasing sleep latency but decreasing sleep efficiency and suppressing delta wave sleep - they make you sleepy, but your sleep sucks.

5HTP, like l-tryptophan, is a serotonin precursor that has been shown in some studies to promote sleep. The presumed mechanism is indirect: 5HTP can cross the blood-brain barrier then be converted into serotonin, which then can bind to serotonin receptors. Of course, some of those receptors can make people sleep while others can wind people up. You can't aim either the 5HTP or serotonin itself at any particular receptors, so it's a bit of a crapshoot. Generally speaking, serotonin's effects of increasing nausea (by binding to 5HT3 receptors both in the brain and in the gut) and of increasing diarrhea (by binding to to receptors in the myenteric plexus and promoting peristalsis) outweigh its effects on sleep.

Neither one of these is something that I'd personally be willing to try.

mstevens,
Thank you for your reply. I have to admit, I'm a little confused by what you said here, so if my answer seems confused, I hope you'll help me understand.

Taking GABA does seem to make people drowsy - not just me. It's the actual molecule -- not a mimic. Something seems to be happening there. It may not have to cross the blood brain barrier. As you suggest, much of our neurological activity is in the gut. Maybe I just need to reach that to have a beneficial effect. And shouldn't it have a more beneficial effect than any mimic?

From wikipedia, I found this quote:

Delta waves can arise either in the thalamus or in the cortex. When associated with the thalamus, they likely arise in coordination with the reticular formation.[6][7] In the cortex, the suprachiasmatic nuclei has been shown to regulate delta waves, as lesions to this area have been shown to cause disruptions in delta wave activity. In addition, delta waves show a lateralization, with right hemisphere dominance during sleep.[8] Delta waves have been shown to be mediated in part by T-type calcium channels.[9] During delta wave sleep, neurons are globally inhibited by gamma-aminobutyric acid (GABA).[10]

[6]^ Gross, Richard E. (1992). Psychology: the science of mind and behaviour. London: Hodder & Stoughton. pp. 112–113. ISBN 034056136x.
[7]^ Maquet, P., Degueldre, C., Delfiore, G., Aerts, J., Peters, J. M., Luxen, A., et al. (1997). Functional neuroanatomy of human slow wave sleep. Journal of Neuroscience, 17(8), 2807-2812.
[8]^ Mistlberger, R. E., Bergmann, B. M., & Rechtschaffen, A. (1987). RELATIONSHIPS AMONG WAKE EPISODE LENGTHS, CONTIGUOUS SLEEP EPISODE LENGTHS, AND ELECTROENCEPHALOGRAPHIC DELTA WAVES IN RATS WITH SUPRACHIASMATIC NUCLEI LESIONS. [Article]. Sleep, 10(1), 12-24.
[9]^ Lee, J., Kim, D., Shin, H. Lack of delta waves and sleep disturbances during non-rapid eye movement sleep in mice lacking a1g-subunit of T-type calcium channels. PNAS;101(52): 18195-18199.
[10]^ a b Hobson, J. , & Pace-Schott, E. (2002). The Cognitive Neuroscience of Sleep: Neuronal Systems, Consciousness and Learning. Nature Reviews Neuroscience, 3(9), 679-693.

From the above quote in blue, I got the impression that GABA instills delta sleep. People with Fibromyalgia often take GABA to help reduce pain during sleep.

In my opinion, sleep docs are only getting part of the story because they're only scanning the brain with eeg. Considering that there is a huge amount of neurological activity happening in the gut, aren't we missing something by not measuring what's going on there?

I've noticed the diarrhea thing with 5-HTP, so I can see why you suggest that is a bit of a crap shoot. Luckily, this effect happens during waking hours and not while I'm masked up.

I have not noticed any nausea from either supplement.

DD, what "GABA" are you taking ?

DreamDiver wrote:Taking GABA does seem to make people drowsy - not just me. It's the actual molecule -- not a mimic. Something seems to be happening there. It may not have to cross the blood brain barrier. As you suggest, much of our neurological activity is in the gut. Maybe I just need to reach that to have a beneficial effect.

Before reaching a conclusion about oral GABA making people drowsy, I'd want to keep in mind that the single most common response to placebo is drowsiness. Placebo responses in the realm of sleep and wakefulness are huge.

DreamDiver wrote:And shouldn't it have a more beneficial effect than any mimic?

Not necessarily. Think, for example, of the effect on pain of morphine, which mimics an endorphin. You have brain receptors for endorphins, not poppy juice. The poppy squeezings work much, much better for pain than any amount of endorphin.

In fact, in general, "mimics" tend to have much stronger effects at receptors than the substances those receptors are used to dealing with.

With GABA it gets messier than usual since there are 3 receptor subclasses (one of which is only in retinas). The one of most interest to us, the GABAA receptor which is the inhibitory one, is a big ol' blob of 5 different protein subunits each of which comes in numerous different versions in different people. The complex has numerous binding sites where different things can bind. Most of the things we use as drugs don't even bind to the GABA binding sites but are allosteric modulators (that bind to a protein and change its shape).

DreamDiver wrote:I got the impression that GABA instills delta sleep. People with Fibromyalgia often take GABA to help reduce pain during sleep.

There's certainly a connection. With neurotransmitters it's far from as simple as "this does that." Think of a neurotransmitter as electricity. Now, does electricity heat your house, or does it cool it? Depends on whether a heater is plugged in or an A/C. Given that both can be plugged in, what matters most is what's turned on (here's where kinins or neuromodulators come in). A transmitter is a signal, but it doesn't "do" anything. Cells do stuff.

DreamDiver wrote:In my opinion, sleep docs are only getting part of the story because they're only scanning the brain with eeg. Considering that there is a huge amount of neurological activity happening in the gut, aren't we missing something by not measuring what's going on there?

I don't think they're missing a thing. Those neurons are pretty much only connected to each other and to muscle cells in the muscle layer of the gut. There's practically no communication to the brain other than sensory data. Your gut will work reasonably well completely disconnected from your brain and your brain will work perfectly well completely disconnected from your gut. All sleep happens in the brain. The brain bone is connected to the gut bone, but I have strong doubts that tickling neurons in the colon has any effect on brain sleep centers. There are people who've had enterectomies (surgical or traumatic removal of the entire gut). I'm not aware that there is any consistent change in sleep that's been associated with this.

Kudos to mstevens.
Yep, I was wrong when I interpreted 5-HTP as 5-HT.

Still concerned about the use of both these substances without a doc giving the ok. Once brain chemistry goes askew, it can be difficult to get it back to "normal".

The brain is the most complicated place I know of. You might want to check this URL. http://www.benbest.com/science/anatmind/anatmd10.html

mstevens wrote:Before reaching a conclusion about oral GABA making people drowsy, I'd want to keep in mind that the single most common response to placebo is drowsiness. Placebo responses in the realm of sleep and wakefulness are huge.

mstevens wrote:

DreamDiver wrote:And shouldn't it have a more beneficial effect than any mimic?

Not necessarily. Think, for example, of the effect on pain of morphine, which mimics an endorphin. You have brain receptors for endorphins, not poppy juice. The poppy squeezings work much, much better for pain than any amount of endorphin.
In fact, in general, "mimics" tend to have much stronger effects at receptors than the substances those receptors are used to dealing with.

I guess it depends on your notion of 'better'. For instance, if I am given morphine or related opiates, my entire bowel system shuts down for a week. It also is a migraine trigger and makes me vomit, even at low doses, if I take more than one dose consecutively.There are other worse things that happen that I won't go into here. I'm not sure 'more' equals 'better'.

mstevens wrote:With GABA it gets messier than usual since there are 3 subclasses (one of which is only in retinas). The one of most interest to us, the GABAA receptor which is the inhibitory one, is a big ol' blob of 5 different protein subunits each of which comes in numerous different versions in different people. The complex has numerous binding sites where different things can bind. Most of the things we use as drugs don't even bind to the GABA binding sites but are allosteric modulators (that bind to a protein and change its shape).

So they don't actually do what GABA does. A good example might be gabapentin, a synthetic analog of GABA that tends to make me, as my sleep doc put it, 'emotionally labile'. In other words, it makes me cry at the drop of a hat. No point in taking that. GABA doesn't do that. As you say, a lot of these synthetics do things other than what the original molecule was intended for. Again, I'm not sure that's always for the best.

mstevens wrote:

DreamDiver wrote:I got the impression that GABA instills delta sleep. People with Fibromyalgia often take GABA to help reduce pain during sleep.

There's certainly a connection. With neurotransmitters it's far from as simple as "this does that." Think of a neurotransmitter as electricity. Now, does electricity heat your house, or does it cool it? Depends on whether a heater is plugged in or an A/C. Given that both can be plugged in, what matters most is what's turned on (here's where kinins or neuromodulators come in). A transmitter is a signal, but it doesn't "do" anything. Cells do stuff.

Could you clarify where you're going with this?

mstevens wrote:

DreamDiver wrote:In my opinion, sleep docs are only getting part of the story because they're only scanning the brain with eeg. Considering that there is a huge amount of neurological activity happening in the gut, aren't we missing something by not measuring what's going on there?

I don't think they're missing a thing. Those neurons are pretty much only connected to each other and to muscle cells in the muscle layer of the gut. There's practically no communication to the brain other than sensory data. Your gut will work reasonably well completely disconnected from your brain and your brain will work perfectly well completely disconnected from your gut. All sleep happens in the brain. The brain bone is connected to the gut bone, but I have strong doubts that tickling neurons in the colon has any effect on brain sleep centers. There are people who've had enterectomies (surgical or traumatic removal of the entire gut). I'm not aware that there is any consistent change in sleep that's been associated with this.

I think we're going to have to agree to disagree here. Even with the vagus system snipped, aren't the majority of neurotransmitters created in the gut? Has there been a thorough study of people with gross enterectomy ruling out its effect on sleep by an actual somnologist? I'm guessing not. I think there is a closer connection between the enteric neural activity and sleep than our current line of inquiry has been able to establish. Maybe it's hard to wire an eeg to entera with its smooth muscle action that the brain doesn't have. I suspect there has been insufficient study for you to be able to fully endorse your statement: "I don't think they're missing a thing."

Samba wrote:DD, what "GABA" are you taking ?

http://www.vitacost.com/NSI-GABA-Gamma- ... tyric-Acid
This is what I'm taking. I certainly wouldn't suggest others take it, and can only relate my personal experience.

Thanks, mstevens, for taking the trouble to post those explanations. Do stick around.