xxxv. Can one figure out one’s own rhythms?

11 July 2007 at 12:57 | Posted in Circadian rhythm | 5 Comments
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This will be a lament, mostly without links unless someone insists. 
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To properly treat Delayed Sleep-Phase Syndrome (DSPS), one should know the patient’s circadian rhythms. At the least, one should know 

  1. when the natural sleep onset and spontaneous wake-up times are,
  2. when the core body temperature minimum, nadir, occurs during sleep, and
  3. when DLMO (dim light melatonin onset) is and preferably also the midpoint of melatonin in the blood.

Treatment with melatonin “supplement”, a hormone, and bright light therapy are very dependent on knowing these things, on getting (guessing) them right.  

One study I found used eight of the usual subjects: normal, healthy young men. Their rhythms were determined in detail before the start of the study. The final report included results for only seven of them. Why? With all possible expertise and equipment at hand, one factor for one of the young men was determined wrongly by half an hour, so they had to leave him out. I’m glad they admit this sort of thing in the report, but it certainly raises the question of how we ordinary, abnormal mortals are supposed to be able to find these things out.  

One study mentions that the period from nadir to awakening varied in their cohort from 1 to 6.5 hours. One found about a half hour difference in the averages for men and for women.  

Well, if patients haven’t messed up their systems entirely with traditional sleeping pills and long-term coping tactics, number 1 above should be possible to identify. 

 Number 2, nadir, is said to be approximately two hours before spontaneous awakening in normal people, longer that that in DSPS people and even longer in people with Non-24. It should occur approximately seven hours after DLMO. Bright light therapy should be used a couple of hours after nadir to advance circadian rhythms. A few hours later than that, according to the phase response curve (PRC) for light in humans, the light will have almost no effect at all. Am I one of those whose nadir is six hours before wake-up?  If so, using my light box is a waste of time and effort. How to know?  It is also not entirely clear that moving the timing of the sleep-phase also will move the timing of the body’s other circadian rhythms, though in theory it should.  

 Then we have number 3 above, the timing of endogenous (natural) and exogenous (supplemental) melatonin. We all have pineal glands which secrete this hormone at night (whenever our own “night” is). Somehow it can make us sleepy and let us fall asleep. The mechanics of that are not yet well understood.  

There appear to be two schools of thought regarding the timing of supplemental melatonin. The first and most common has been mentioned before. One uses it almost as one would a sleeping pill, a hypnotic in the jargon, one-half to two hours before one wants to go to sleep. This works pretty well for me with 0.5 mg melatonin making me sleepy after about one and one-quarter hours. When I get sleepy, I must get to bed immediately as the effect wears off quickly and I can then stay up til all hours.

It’s hard to find much on the second theory, supplemental melatonin as a chronobiotic, though I see that Wikipedia now tells about the PRC for melatonin as well as the PRC for light, and I’ve seen abstracts from two small studies. One of them, here comes a link to an abstract, in 2005, was done on thirteen DSPS patients in Illinois, USA. Melatonin supplements were tried between 1.5 and 6.5 hours before DLMO (dim light melatonin onset). DLMO is generally considered to occur approximately two hours before bedtime. The study results showed that the earlier melatonin was administered, the greater was the advance in the timing of DLMO. Sleep onset was also advanced some, though to a lesser degree.  

 The other study at a different medical center in Illinois, also in 2005, on normal subjects both male and female, suggests that one should use melatonin much earlier than the traditional timing and “in doses small enough not to feel tired right away” to effectively advance one’s circadian rhythms. They experimented with placebo, with 0.5 mg melatonin five hours before bedtime and with 3 mg administered seven hours before bedtime.  Each of the three groups was also treated with bright light in the morning. They conclude that a nearly one-hour advance, daily, in sleeping time <and> light exposure <and> administration of melatonin did not lead to misalignment of circadian rhythms during the three days of the study.

These are but two studies experimenting with the concept of the PRC for melatonin. If the theory proves to be valid, we can expect to see many more in years to come. This should be interesting to follow, and we can hope for some studies which will last longer than three days!

I still lament. When is my temperature minimum? My DLMO? Is it possible for me to advance these and all the other rhythms in alignment and keep them there, without detrimental effects on physical and mental health? The more I learn, the less clear it all becomes. Sigh.


Next:  xxxvi. PRC for melatonin


ix. Melatonin and the effect of light

26 November 2005 at 16:49 | Posted in Circadian rhythm | Leave a comment
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Oops, sorry.  Got a little ahead of myself there.  Melatonin should have been explained before that more technical stuff.
Melatonin is a hormone produced and secreted by the pineal, a tiny, midbrain gland which doesn’t seem to have any other tasks.
The pineal takes its orders from a nearby organ which Mary Poppins surely should have sung about, the suprachiasmatic nuclei.  However you choose to pronounce that, it’s a whole dance tune in itself.  The SCN (for short) is our central biological clock.  If totally isolated from outside cues about time, it will keep running on its own “almost a day” (= circadian) cycles virtually indefinitely.  Cells from mammalian SCN do so, in fact, in a dish.  
The body clock needs to be reset daily.  The SCN receives (or receive, if you prefer) information from the retina directly along a pathway called the retino-hypothalamic tract.  And yes, the SCN is located in the hypothalamus, in the brain. 
The vital information which the SCN processes, is sent to it by special light-sensitive cells in the retina in the back of the eye.  This information about light received at the retina has nothing to do with vision.  It tells our system when day and night are.  There can be other cues as well, such as mealtimes and activities, but light is by far the strongest.  
The rhythms of core body temperature (CBT) and melatonin secretion, at the least, need to be coordinated with each other and with the cycle of light/dark to allow us to fill our need for one long sleep-session, preferably at night.  
The level of melatonin in the blood during the (subjective) day is (or should be) near zero.  As CBT falls during an individual’s night, then starts rising again about two hours before wake-up time, our melatonin level rises during the first half of the night, to drop off during the second.  However, the two curves are not mirror images of one another.  The melatonin level rises quite sharply and then stays on a plateau.  It starts falling a couple of hours before the CBT bottoms out.  Here’s how this is shown in post no. xiii:  


Bright light banishes melatonin from the blood and stops / delays the secretion of it.  

A person with a normal circadian system who cooperates with nature’s signals will sleep at the same time every night.  The schedule might look like this:

  • 8 or 9 p.m., melatonin secretion starts, perhaps not measurable yet (DLMO, Dim Light Melatonin Onset)
  • 10 p.m., calming down, lights are dim
  • 10:30, feet are hot, person feels sleepy
  • 11 p.m., asleep
  • 3 a.m., melatonin level starts receding
  • 5 a.m., core body temperature minimum
  • 7 a.m., wake up, and light exposure banishes the remainder of the melatonin 

We all know people who’d rather sleep 10 p.m. to 6 a.m. or midnight to 8 a.m.  Those schedules are within the normal range.  

When I was a kid, medicine and science thought that the normal range should be achievable for everyone.  It is not.


Next:  x. Other animals


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