5-HTP : Modes of Action?

I've previously conducted two experiments with 5-HTP: 

5-HTP and its effect on my AHI and sleep in general (link)

5-HTP and its effect on my snoring profile (link) 

Both gave encouraging results. In fact they were so encouraging and surprising that I really would like to know more about how it has the effect that it does, and would it work for other people?

My studies are so small (as I am only experimenting on myself) and the potential for a pharmaceutical solution to Sleep Apnoea and Snoring so attractive that I would love to see further research and a larger trial for 5-HTP as it poses so many questions:

• Does it work for anyone other than me?
• Is it only effective for Mild Obstructive Sleep Apnoea?
• How dose-dependent are the effects? Does too high a dose limit the effectiveness (as with Melatonin)?
• Does the positive effect fade with long-term use?
• Are there any negative effects?
• Are the co-factors that I've been taking with this brand of 5-HTP (label from manufacturer's website here) partly responsible for the effect?

Although I can't find the results of any direct studies looking at AHI or snoring, there is a fair amount of medical literature relating to Serotonin (which 5-HTP is an immediate precursor to, that is 5-HTP is metabolised into Serotonin by the body).

From the existing literature I've tried to piece together possible mechanisms for the effects that I've observed.

THE EFFECTS OF SEROTONIN ANTAGONISTS IN AN ANIMAL MODEL OF SLEEP-DISORDERED BREATHING

By blocking serotonin activity in a breed of dog prone to obstructive apnea, it was possible to induce snoring whilst they were awake along with a collapse of the upper airway, which was reversed when serotonin activity was allowed to return.

Veasey SC, Panckeri KA, Hoffman EA, Pack AI, Hendricks JC
http://ukpmc.ac.uk/abstract/MED/8564132

"Veasey et al" blocked the action of serotonin (5-HT) in Bulldogs while they were awake (using agents known as 5-HT Antagonists). Daytime snoring was observed. Furthermore using live CT scanning a collapse of the upper airway was observed. These effects were reversed when the action of serotonin was unblocked.

This gives a clear indication that serotonin is essential for maintaining the muscle tone of the upper airway.

So, why does this tone drop off during sleep? During sleep (and especially during REM sleep) muscle tone is reduced. In REM sleep we undergo muscle atonia (deactivation of most muscles - this is also the cause of sleep paralysis). It is also shown that Serotonin activity is at its lowest during REM sleep. So a greatly reduced level of serotonin activity leads to a greatly reduced level of muscle activity during REM sleep.

It doesn't seem that simply activating certain Serotonin receptors can undo this muscle atonia. This is a bit of a leap on my part, but it seems that 5-HTP excites all types of serotonin receptors rather than just a few that are excited by various other pharmaceutical methods. Maybe this is because that by allowing the body to convert the extra 5-HTP to serotonin you are allowing natural metabolism of 5-HTP to 5-HT rather than just a localised or specific 5-HT receptor activity.

There are papers that support the fact that 5-HTP has an effect where 5-HT has none (albeit in motor function).

5-HT PRECURSOR LOADING, BUT NOT 5-HT RECEPTOR AGONISTS, INCREASES MOTOR FUNCTION AFTER SPINAL CORD CONTUSION IN ADULT RATS

Y. Hayashi, S. Jacob-Vadakot, E.A. Dugan, S. McBride, R. Olexa, K. Simansky, M. Murray, &  J.S. Shumsky

Exp Neurol Jan 2010

We conclude that selective 5-HT or 5-HT receptor activation was not effective in improving 2C1A hindlimb function after incomplete lesions. In contrast, the 5-HT precursor 5-hydroxytryptophan (L-5-HTP), which activates all classes of 5-HT receptors, increased both %WS and hindlimb activity

http://ukpmc.ac.uk/abstract/MED/19840787

In the following paper by Ling, Bach & Mitchell it is shown that 5-HTP has the ability to reveal and activate a latent pathway in the spinal cord in hemisected rats (similating an incomplete spinal injury).

SEROTONIN REVEALS INEFFECTIVE SPINAL PATHWAYS TO CONTRALATERAL PHRENIC MOTONEURONS IN SPINALLY HEMISECTED RAT 

Liming Ling, Karen B. Bach, Gordon S. Mitchell

Exp Brain (June 1994)

These results indicate that serotonin converts ineffective crossed phrenic pathways in the spinal cord to effective pathways. It remains to be determined whether serotonin is both necessary and sufficient in this modulatory process, or if it is a nonspecific result of increased phrenic motoneuron excitability.

http://ukpmc.ac.uk/abstract/MED/7843300

5-HYDROXYTRYPTOPHAN-INDUCED RESPIRATORY RECOVERY AFTER CERVICAL SPINAL CORD HEMISECTION IN RATS

Shi-Yi Zhou & Harry G. Goshgarian

J. Applied Physiol (June 2000)

Because experiments were conducted on animals subjected to C2 spinal cord hemisection, the recovery was most likely mediated by the activation of a latent respiratory pathway spared by the spinal cord injury. The results suggest that serotonin is an important neuromodulator in the unmasking of the latent respiratory pathway after spinal cord injury. 

http://ukpmc.ac.uk/abstract/MED/11007592

So we have two potential mechanisms by which 5-HTP could work: 

1. By loading with 5-HTP it allows the body to metabolise it to 5-HT activating all classes of 5-HT receptors thereby reducing the effects of muscle atonia in REM without completely inhibiting REM atonia.
2. By possibly activating a dormant pathway in the spine to the phrenic nerve (increasing breathing effort). 

As we've seen by my sleep-study results, my sleep apnoea is obstructive in nature, so it is unlikely that increasing breathing effort would reduce my AHI as I still make breathing movements but they are rendered ineffective by the obstruction in my upper airway.

If 5-HTP does work in these two ways then it's possible that 5-HTP may have a positive effect on both Obstructive and Central sleep apnoea as item 1 above relates to OSA while item 2 relates to some forms of CSA. 

Electric Blankets

I'm posting this because it has me puzzled. As always, I'd love feedback and people's thoughts please, either in the comments section of this blog or via Twitter @Hypnagog

After seeing that my temperature dropped in REM sleep and caused me to wake up, I decided to get hold of an electric blanket to see if that could go some way to stabilising my temperature at night.

Before I carry on, this post is not an attack on electric blankets, nor their manufacturers, and I post the following findings as inconclusive and for discussion.

I fitted the blanket beneath my bedsheet, switched it on to preheat the bed (as shown in the instructions), then got into bed and turned it onto a maintenance setting.

I remember during the night that I was warm, too warm. I remember leaning over and turning it down to its lowest setting and still being uncomfotable, but I did sleep, and from memory it was most of the night.

However...

When I looked at the Zeo data I found that I had almost no REM (5 mins) and that it was replaced by wake.

I was tired when I woke, so it seems to fit. REM rebound the following evening wasn't significant, although I did enter REM before SWS.

Possible Causes?

I did wonder if the electromagnetic field given off by the blanket could have either affected me, or the Zeo's detection of REM. 

Akerstedt et al (1999) showed that a 50-60Hz field can distrupt sleep with all of the following reduced: total sleep time (TST), sleep efficiency and stages 3+4 slow wave sleep (SWS). However, REM wasn't reduced.

It could be that with such a disturbed night there was little chance of hitting REM but that seems unlikely to me as my experiment with REM deprivation shows that REM is desparate to occur (and can even happen at sleep onset if severely deprived).

I do have a couple of Gauss Meters, so the following evening I checked the blanket out. Admittedly this was with the blanket up to it's highest setting (a setting that you would only use for pre-heating, not sleeping), but as expected there is an electromagnetic field around the blanket.

The blanket didn't give off a field until I placed my hand on it (simulating someone laying down on it).

This is no surprise as everything gives off an EMF field: low energy lightbulbs, microwaves, TVs, computers, WiFi, even us to a degree. This isn't going to turn into a jumping up and down blog post demanding that we all live in Faraday Cages but I did wonder if there was an link.

If EMF is to blame, then my instinct says that the blanket affected the measurement of REM rather than the REM itself.

Another possibility is that there is a link between reduced REM and increased body temperature, such as in the case highlighted here (a fever causing reduced / disturbed REM sleep).

Could it just be that the temperature disturbed me during the night, after all I do like the bedroom to be cold?

If I had to guess why this would only happen in REM, I would have to speculate that this is because the body doesn't regulate its temperature well during REM and becomes largely poikilothermic, so rather than waking because I was too cold, I was waking because I was too warm. This would suggest that I did go into REM but that it was too fragmented to be detected by the 30 second epoch of the Zeo. I would suggest that REM that is that fragmented is next to useless as far as restorative sleep is concerned.