53. Light therapy: white, blue or maybe green?

30 May 2010 at 14:00 | Posted in Circadian rhythm | 3 Comments
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It has long been known that light and dark affect the daily as well as seasonal rhythms of living things.  Early in the 1900s it was assumed that humans’ daily rhythms were less affected than those of “lower” beings, but that attitude was proved wrong.

In the 1980s it was noted that some totally blind people entrained perfectly to the 24-hour cycle while many did not.  Until some time in the 1990s, it was not known if entrainment occurred by light to the eyes or to the skin.  One research team claimed to have proven that light to the backs of the knees effected entrainment, but neither they nor other researchers could duplicate those results, which later were withdrawn.

It is now clear that we and other animals entrain primarily by light to the eyes, though secondary cues such as social activity, feeding times etc. also play a role.  It is also clear that our eyes contain not only rods and cones for vision but also the recently discovered light sensitive ganglion cells for the entrainment of circadian rhythms.  The light sensitive pigment in these cells is melanopsin.

There it stands, but there are always new questions to be answered.  One is: 

Do the light sensitive ganglion cells contribute to vision,

and do the rods and/or cones contribute to

the non-visual effects of light?

If the ganglion cells’ photosensitivity contributes to vision at all, it is very minimally.  But a study* published this month by well-known researchers suggests that the cones do affect entrainment, with variations dependent on the timing and intensity of the light.  The practical implications include the question of whether the use of blue-blocking goggles in the evening, so-called “dark therapy”, really does allow normal flow of melatonin as intended.  [An aside: mightn’t there be a more direct way to find this out?]   In addition, the jury is still out on what color light – white, blue or perhaps green – is best to use in light therapy.

In this study in Boston, more than 50 human subjects each spent 9 days in an laboratory environment free of time cues.  Semi-recumbent, totally confused about the time of day, and with their melatonin rhythms individually determined, half of them were exposed to blue (460nm) light and half to green (555nm) for 6.5 hours starting shortly after their own melatonin secretion started. 

It is well-known that blue light (including about 460 to 482nm) excites melanopsin leading to the suppression of  melatonin.  The question here is whether the green light may have similar or equal effects. Green was chosen because the human visual system is most excitable at green (555nm).

In the figure, A and B are two subjects.  Each person’s normal pattern of melatonin secretion is repeated on the left and on the right in black.  On the left, blue light acutely suppresses A’s melatonin, while green light only delays B’s for a good hour.  The next night, as we see on the right, the pattern of melatonin secretion has been phase-shifted by the previous night’s light exposure about equally for the two subjects (horizontal red line).  From previous knowledge, one would have expected an appreciably greater delay after the blue light than the green.

The authors write: 

“Our data … raise the possibility that activation of cone photoreceptors in the late evening by relatively low-illuminance light sources, such as liquid crystal display monitors, table lamps, and dimmable lamps, may delay the circadian clock and therefore contribute to the high prevalence of delayed sleep phase disorder.” [My emphasis.]

and

“[B]locking short-wavelength light with blue-blocking goggles may not always be effective in preventing undesired circadian responses based on our finding that longer-wavelength light is able to induce robust phase-shift responses.”

and

“Our findings have implications for the development and optimization of light therapies for a number of disorders, including circadian rhythm sleep disorders.…”

* Spectral Responses of the Human Circadian System

Depend on the Irradiance and Duration of Exposure to Light.

Joshua J. Gooley, Shantha M. W. Rajaratnam, George C. Brainard,

Richard E. Kronauer, Charles A. Czeisler and Steven W. Lockley

Science Translational Medicine, 12 May 2010 

See also these older posts: 

xliii. Blindfolding the blind   

xliv. Rods and cones and the “new” ipRGC 

 (posted by D )

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Next post:  #54. Take a Nap!

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xlix. 2009: sleep logs

4 February 2010 at 22:53 | Posted in Circadian rhythm | 18 Comments
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As “D” gets the forms filled out, her (my) sleep logs will appear here.  They are of interest primarily to myself and my sleep specialist, Prof. Holsten.  But if you see a long-term pattern, do let me know.  What I see for sure is that I am affected by melatonin and/or bright light.  Next experiment will be to cut the melatonin and see what just morning bright light does.

Sleep Diary

Sleep Diary

The doctor said: "WHAT happened here?"

Umm, I just tried a couple of weeks without melatonin and light therapy, is all.  

More weeks free of melatonin

Back on track

Back on track, such as it is.  My “normal” with the help of melatonin and light therapy.

Posted by Delayed2Sleep (aka “D”).  Updated 22 February 2010.

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Next post:  l.  A Man with Too Long a Day (by L)

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xli. Coincidence & update

6 June 2009 at 23:50 | Posted in Circadian rhythm | Leave a comment
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Chapter three begins a year-to-the-day after the end of Chapter two.   A coincidence.  (I so wanted to call it serendipity but don’t want to add to the misuse of that word.)

In this last year I’ve retired but kept on with melatonin at night, my light box in the “morning” and keeping my sleep diary every day.  Plus a tiny dab of melatonin late afternoon and yellow goggles in the evening, when I don’t forget. 

The schedule has not become as regular as I’d thought and hoped, even though wake time is preferably “by 1 p.m.”  About every other month the  sleep specialist reminds me that he, at the beginning, had said that he couldn’t promise regularity, a “cure”.  And that he thought that my circadian period is “upwards of 28 hours”.

After five years of daily melatonin, I tried eight weeks without, thinking that, given the chance, my system might land on its own schedule.  Nope.  Those sleep diaries show chaos:  sleep whenever, rarely for 3-4 hours, often for 12-14 hours, night or day.  When I happened to get up between 9 a.m. and 2 p.m. I did use the light box.  There’s no sign of a system, most particularly not any sign of Non-24, for which I’m glad.  When I showed the diary to the specialist, he pointed at those eight weeks and asked: “What  happened here?”

It took only a few days back on melatonin to get back where I was before; here’s a typical 4 weeks:

4weekDIARY jpeg

BTW, as you can see, the sleep diary is now simplified, with four weeks to the page.  With 28 days across and 24 hours down, midnight in the middle as before, symbols at the top for melatonin use and at the bottom for use of light box, the filled in sleep parts of each column show clearly how (ir)regular my sleep pattern is.  Illustrated is, believe it or not, a month that the specialist was quite happy about:  “That may be the best month you’ve had.”

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Next:  xlii. Researchers mentioned here

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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. 
 
~ ~
 

~ ~

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.

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Next:  xxxvi. PRC for melatonin

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xxxi. Light Therapy Recommendations, 1999

23 February 2007 at 11:47 | Posted in Circadian rhythm | Leave a comment
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Continued from the previous entry. From a 1999 article.

 RECOMMENDATIONS FOR SPECIFIC DISORDERS:

1. Delayed Sleep-Phase Syndrome (DSPS) 

2.  Advanced Sleep-Phase Syndrome (ASPS)

3. Non-24-Hour Sleep-Wake Syndrome (NON-24)

 

1. DSPS

Delayed sleep-phase syndrome is a disorder in which the major sleep episode is delayed in relation to the desired clock time. It results in symptoms of sleep-onset insomnia and/or difficulty in awakening at the desired time. Core body temperature minimum and peak of the melatonin rhythm are shifted to later in the morning than normal.

Treatment Objectives and Indications 

Based on the human PRC, a phase-advance will take place if the subject is exposed to light after the peak of melatonin rhythm or the minimum of core body temperature, usually in the early morning.

a) Light therapy appears to have potential utility in the treatment of DSPS.

For use of light therapy in the treatment of DSPS, 2000 to 2500 lux from 6 to 9 a.m. and optionally wearing dark goggles from 4 p.m. to dusk is an approach that has been studied with apparent effectiveness. However, some patients will have a temperature minimum during or after this light exposure time period and may not respond or respond paradoxically with a phase-delay rather than a phase-advance. In those patients who do not respond as expected and in whom information such as sleep diary entries or, if available, melatonin rhythm or core body temperature suggests a peak rhythm or core body temperature minimum at a time after the exposure to light therapy, a later morning time period for light therapy (e.g., after 9 a.m.) may be tried.

b) The minimum or optimal duration of light therapy for DSPS is unknown.  

In one study, 12 days of bright light was successful in shifting core body temperature and improving sleep efficiency and was rated better than dim light. In addition, the duration of therapy necessary to provide continuing effectiveness is unknown as is the possibility of tolerance (i.e., loss of benefit over time) to the therapy.

2. ASPS

Advanced sleep-phase syndrome is a disorder in which the major sleep episode is advanced in relation to the desired clock time.  It results in symptoms of compelling evening sleepiness, an early sleep onset, and an awakening that is earlier than desired. Core body temperature minimum and peak melatonin rhythm occur earlier in the morning than usual.

Treatment Objectives and Indications

Based on the human PRC, a phase-delay will take place if the subject is exposed to light soon after the dim light melatonin secretion onset or core body temperature maximum, usually in the evening.

a) Light therapy appears to have potential utility in the treatment of ASPS.

For the use of light therapy in the treatment of ASPS, 2500 lux for four hours from 8 p.m. to midnight, or 4000 lux for two or three hours from 8 or 9 p.m. to 11 p.m. are approaches that have been studied with apparent effectiveness.  However, some patients may have a temperature maximum substantially before this time period and may not respond with a phase-delay.  In those patients exposure to light at an earlier time period may be attempted.

b) The minimum or optimal duration of light therapy for ASPS is unknown.

In one study 25 days of bright light was successful in shifting core body temperature and improving sleep efficiency and performance.  In addition, the duration of therapy necessary to provide continuing benefit is unknown as is the possibility of tolerance (i.e., loss of effectiveness over time) to the therapy.

3. NON-24 

Non-24-hour sleep-wake syndrome is a syndrome in which patients fall asleep at a different time each day because the circadian period differs from 24 hours.  For example, on day one the patient may fall asleep at 10 p.m., day two at 12 midnight, day three at 2 a.m. etc. Patients may have either insomnia or hypersomnia depending on which phase of the circadian cycle they are in when trying to sleep. Core body temperature cycles may be greater in length than normal. Blind individuals are a special case since the normal sleep-wake cycle may be longer than 24 hours and if no light reaches the SCN, there may not be natural resetting of the circadian clock to 24 hours. Totally blind individuals, such as those whose eyes have been enucleated, comprise a minority of the legally blind. These individuals will have no retinal response to light and may have free-running circadian rhythms. Light therapy is of no confirmed benefit in these patients. However, some blind individuals who have this syndrome may be responsive to light therapy despite no apparent perception of visible light.

Treatment Objectives and Indications

Currently there are very few studies on which to base a strategy but some reports suggest that morning light may work. Other studies are negative. Based on the phases of the light PRC, a phase-advance will take place if the subject is exposed to light at a time soon after the peak melatonin rhythm or the core body temperature minimum in the morning, which would regularize the circadian cycle to a more typical sleep/wake cycle. However, care needs to be taken to ensure that the patient is not in a portion of the PRC such that the morning light exposure occurs after the dim light melatonin secretion onset or the core body temperature maximum and before the temperature minimum or peak melatonin rhythm. In such a case, there could be no response or a phase-delay.

a) Light therapy may be of benefit in treating some blind patients with non-24-hour sleep-wake syndrome.

For the use of light therapy in the treatment of non-24-hour sleep-wake syndrome, 3300 lux for one hour between 6 and 8 a.m. is an approach that has been studied with apparent effectiveness for blind persons. No recommendation for sighted individuals is made since insufficient data is available. If the expected response does not occur, an adjustment of the timing of the light exposure may be attempted to produce the phase-advance or phase-delay, depending on information such as sleep diary entries or, if available, core body temperature maximum or minimum or dim light melatonin secretion onset or the peak of the melatonin rhythm.

b) The minimum duration of light therapy for non-24 hour sleep-wake syndrome is unknown.

In one study 14 days of bright light was successful in improving symptoms and increasing melatonin secretion. In addition, the duration of therapy necessary to provide continuing effectiveness is unknown as is the possibility of tolerance (i.e., loss of effectiveness over time) to the therapy.

 FOR SYNDROMES ASSOCIATED WITH PHASE ADVANCES AND DELAYS, LIGHT THERAPY APPEARS TO HAVE CLINICAL UTILITY.

 

 My doctors didn’t know that in 1999.

Did yours?

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Next:  xxxii. Chronotherapies for DSPS

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