Resetting the Circadian Clock: Yes, I am... - Cure Parkinson's

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Resetting the Circadian Clock

Bolt_Upright profile image
9 Replies

Yes, I am kind of spitballing here. Could resetting the circadian rhythm help with PD?

I posted this a couple days ago: Treatment of isolated REM sleep behavior disorder using melatonin as a chronobiotic 2021 onlinelibrary.wiley.com/doi... The whole protocol is based on using a combination of 2 mg slow release melatonin and a rigid bedtime schedule to reset the circadian rhythm.

And then stumbled across this: Homotaurine in Parkinson's disease 2015 pubmed.ncbi.nlm.nih.gov/258... "Our data suggest a beneficial effect of homotaurine on excessive sleepiness. Future studies are encouraged to confirm this promising role of homotaurine in promoting the sleep/awake cycle in patients with PD". So Taurine helps promote a sleep/awake cycle? I am moving my Taurine/NAC combo to take it along with my Melatonin 30 minutes before bedtime (this timing may be unnecessary).

And then I found this: Taurine Treatment Modulates Circadian Rhythms in Mice Fed A High Fat Diet 2016 ncbi.nlm.nih.gov/pmc/articl... "Taurine normalized the gene and protein expression of PER1 in beta-cells, which suggests that it could be beneficial for the correction of daily rhythms and the amelioration of obesity and diabetes." "However, it is clear from the present study that taurine improves disturbances in the 24 h pattern of plasma insulin and leptin, as well as Per1 expression in pancreatic islets caused by HFD feeding. Thus, this is the first evidence that shows that taurine could be a potential target to correct or ameliorate the disturbances in circadian rhythms caused by obesity."

And finally a quick Google for ways to reset the Circadian Rhythm: Circadian Rhythm Sleep Disorders my.clevelandclinic.org/heal...

If you Google this "circadian rhythm parkinson's disease" you will see plenty of evidence that PwP have messed up Circadian Rhythms.

I may be grasping at straws, but if (per the first link) people actually recovered from REM Sleep Behavior Disorder and most did not progress to PD, then getting to bed at the same time every night, at a reasonable time, seems like something worth trying.

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JBOVERT profile image
JBOVERT

HI BOLT GOODMORNING,YES I BELEIVE that resetting your circadium clock is a great benefit to anyone so inclined and based on my own experience it has proven to be a great way to balance my daily activity schedule. right now for me i seem to needing to lay down during the day and the frequency that this happens is creating a problem for my sleep/wake balance so its necessary for me to reset my circadium clock on a regular bass. its pretty easy to do just go outside at around the sunrise time of day and just a glance in the direction of the sun is what it takes so you can get just a chard of sunlight into your pineal gland and youre good to go...I can actually feel the effects of the sun energy it energizes me...

wriga profile image
wriga in reply to JBOVERT

Hi Bolt, JBovert,

I'm beginning to accumulate a whole mass of information on the circadian rhythm (CR) and its links to PD. It's absolutely fascinating.

The CR creates the most efficient way to resolve oxidative stress and mitochondrial dysfunction in neurons by providing the response to these problems in terms of enzymes and antioxidants at just the right time of day (morning for humans) and winding down these processes when we don't need them (overnight).

To do this, in healthy subjects the natural production of Nrf2 follows the CR and eliminates oxidative stress in real time. However the magnitude of the CR is reduced in older people (less melatonin at night and less cortisol and Nrf2 in the morning). For PwPs, the CR is further compromised (loss of both magnitude and phase). This of course disrupts sleep and creates daytime fatigue, but also means that there is no optimal time frame to eliminate oxidative stress, since the sleep/wake cycle is fragmented.

The natural production of dopamine is closely aligned to the CR since the synthesis of tyrosine hydroxylase (HT), the enzyme that makes dopamine from l-tyrosine in dopaminergic neurons also strictly follows the CR. As one of the many feedback loops, dopamine is involved in modulating the CR.

What caught my attention when digging into this subject, thanks to a nudge from Bolt, is that every process or molecule involved in the CR plays a role in the management of oxidative stress and vice-versa.

You might be tempted to think that this is a minor issue. It is not. The magnitude of the diurnal changes are very important. For HT for example, the variation is x2 in healthy people.

The loss of the CR in PwPs is therefore a major factor in the disease.

The CR is driven by a primary clock in the brain and secondary clocks in peripheral organs. To work properly, they all have to be synchronized.

The primary clock gets its timing and magnitude cues from light. For wild animals and prehistoric humans, these light messages come from the sun because they spend their time ooutside.

The light messages come through the retina via the different light receptors. The range is from approximately 0.01 Lux (moonlight) to 100, 000 Lux (full sunlight),, a range of 10 million.

Some of these receptors make images, others measure the light intensity and send that information to the primary clock.

Even on a cloudy winter's day like today, the outside light intensity is between 3000 and 7000 Lux. In summer it ranges from 10000 to 150000. The light spectrum is also important. The receptors that measure high intensity natural daylight to reset the CR clock are centred on blue light at 480 nm. This is the peak wavelength of daylght in the early morning and late afternoon. These extreme measurements of light intensity fix the extreme time points of the CR. Also these 480 nm clock sensors only measure average light intensity over long periods. Count on at least one hour. There's no quick fix.

Modern humans no longer get these cues. Lighting in people's homes is in the range 30 to 70 lux. That is 100 times less than outdoors and is what our clock receptors see in the morning and evening. Many people never get beyond this range for days. Also, indoor incandescent lighting is especially weak near the 480 nm wavelength, although modern cold white led lights are better.

This is now being recognised as a major health issue especially in retirement homes where some residents never go outside.

So JBovert is right, to boost your CR, and improve your sleep pattern, you must go outside in strong daylight in the early morning and early evening for at least one hour, even in winter.

Bolt_Upright profile image
Bolt_Upright in reply to wriga

You know, the couple of success stories about stopping PD that I have read are people that started living a simple life of outside work.

Bolt_Upright profile image
Bolt_Upright in reply to wriga

Can I sit in front of a window for an hour if it is facing the sun?

Bolt_Upright profile image
Bolt_Upright in reply to wriga

Based on your wonderful post, something just occurred to me: The Association Between Vitamin D Status, Vitamin D Supplementation, Sunlight Exposure, and Parkinson’s Disease: A Systematic Review and Meta-Analysis ncbi.nlm.nih.gov/labs/pmc/a...

Conclusions: Insufficiency and deficiency of 25-hydroxyvitamin D and reduced exposure to sunlight were significantly associated with an increased risk of Parkinson’s disease. However, vitamin D supplements resulted in no significant benefits in improving motor function for patients with Parkinson’s disease.

It occurred to me that everybody seems to assume that the relationship to lack of sunshine and PD is the subsequent lack of vitamin D. Per your awesome post Albert, it might have nothing to do with vitamin D. It might be all about sunlight resetting the circadian rhythm. That may be why vitamin D supplements make no difference.

chartist

chartist profile image
chartist in reply to Bolt_Upright

Bolt,

Sunlight has the ultraviolet rays that interact basically with cholesterol in the skin to assist in the process of generating vitamin D in the body, but sunlight also has infrared light which can help repair mitochondria (think of one activity of Photobiomodulation and the infrared red light therapy frequently discussed on this forum) and in a recent study is suggested to increase depleted melatonin in the mitochondria as well.

This is one possibility why some people mention "feeling better" when getting full body moderate sun exposure. These same people likely would say they do not get a similar feeling from vitamin D at any dose. Repairing mitochondria as red light therapy is suggested to do should result in increased ATP production and that seems highly likely to make a person "feel better" as well as promote health. Melatonin produced in the mitochondria is not thought to have the same circadian effect as melatonin produced and excreted by the pineal gland and is also not thought to have the same effect on sleep. Infrared radiation is the greatest component of the sun's radiation and yes, sunlight delivers the same beneficial red light range as the expensive devices and at similar and greater mw levels . Our bodies have adapted to the full light spectrum that the sun delivers, not to specific levels such as the 600 to 900 nm range used in red light therapy. The sun is likely the "Ultimate Photobiomodulation" creation and it is free. This could potentially explain why men who work outdoors are up to 28% less likely to develop PD.

Art

JBOVERT profile image
JBOVERT in reply to wriga

Riga,i think that 15 minutes will be suffucient not an hour'

wriga profile image
wriga

Sunlight, or more accurately daylight, has the potential to be beneficial for everyone. Bolt's analysis of the vitamin D story makes sense. As soon as you go outside, daylight enters your body either through the skin or the retina and interacts with our biological processes. We have evolved to make use of s wide range of wavelengths. The peak energy is at 480 nm, blue, which we use as the main input to fix the CR. The visible range, 400 - 700 nm is used to create images. But most energy is delivered by the broad infrared bands which are invisible to our eyes but keep us warm and as recently discovered, provide energy to mitochondria. Since daylight follows a 24 hour cycle, our biological system has developed to take advantage of this abundant source of energy.

By staying indoors we deprive ourselves of this resource.

Going off at a tangent but I wonder if this fits in any way with the difference in skin that PWP have? We are more prone to skin cancer and on a personal note, I'm sure I have lost pigmentation (not just in my substantia nigra). Do PWP absorb sunlight differently? Maybe we don't react normally to daylight. Just a random thought.

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