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Melatonin and the electron transport chain

nanonug

Senior Member
Messages
1,709
Location
Virginia, USA
(Given the importance of the electron transport chain in mitochondrial oxidative phosphorylation, taking melatonin every night might be a good idea.)

https://www.ncbi.nlm.nih.gov/pubmed/28785805

Abstract
Melatonin protects the electron transport chain (ETC) in multiple ways.
It reduces levels of ·NO by downregulating inducible and inhibiting neuronal nitric oxide synthases (iNOS, nNOS), thereby preventing excessive levels of peroxynitrite. Both ·NO and peroxynitrite-derived free radicals, such as ·NO2, hydroxyl (·OH) and carbonate radicals (CO3·-) cause blockades or bottlenecks in the ETC, by ·NO binding to irons, protein nitrosation, nitration and oxidation, changes that lead to electron overflow or even backflow and, thus, increased formation of superoxide anions (O2·-). Melatonin improves the intramitochondrial antioxidative defense by enhancing reduced glutathione levels and inducing glutathione peroxidase and Mn-superoxide dismutase (Mn-SOD) in the matrix and Cu,Zn-SOD in the intermembrane space. An additional action concerns the inhibition of cardiolipin peroxidation. This oxidative change in the membrane does not only initiate apoptosis or mitophagy, as usually considered, but also seems to occur at low rate, e.g., in aging, and impairs the structural integrity of Complexes III and IV. Moreover, elevated levels of melatonin inhibit the opening of the mitochondrial permeability transition pore and shorten its duration. Additionally, high-affinity binding sites in mitochondria have been described. The assumption of direct binding to the amphipathic ramp of Complex I would require further substantiation. The mitochondrial presence of the melatonin receptor MT1 offers the possibility that melatonin acts via an inhibitory G protein, soluble adenylyl cyclase, decreased cAMP and lowered protein kinase A activity, a signaling pathway shown to reduce Complex I activity in the case of a mitochondrial cannabinoid receptor.
 

nanonug

Senior Member
Messages
1,709
Location
Virginia, USA
(In addition, it seem mitochondria are able to uptake exogenous melatonin. Good news!)

Mitochondria: Central Organelles for Melatonin's Antioxidant and Anti-Aging Actions


Abstract
Melatonin, along with its metabolites, have long been known to significantly reduce the oxidative stress burden of aging cells or cells exposed to toxins. Oxidative damage is a result of free radicals produced in cells, especially in mitochondria. When measured, melatonin, a potent antioxidant, was found to be in higher concentrations in mitochondria than in other organelles or subcellular locations. Recent evidence indicates that mitochondrial membranes possess transporters that aid in the rapid uptake of melatonin by these organelles against a gradient. Moreover, we predicted several years ago that, because of their origin from melatonin-producing bacteria, mitochondria likely also synthesize melatonin. Data accumulated within the last year supports this prediction. A high content of melatonin in mitochondria would be fortuitous, since these organelles produce an abundance of free radicals. Thus, melatonin is optimally positioned to scavenge the radicals and reduce the degree of oxidative damage. In light of the "free radical theory of aging", including all of its iterations, high melatonin levels in mitochondria would be expected to protect against age-related organismal decline. Also, there are many age-associated diseases that have, as a contributing factor, free radical damage. These multiple diseases may likely be deferred in their onset or progression if mitochondrial levels of melatonin can be maintained into advanced age.


 

Hip

Senior Member
Messages
17,808

nanonug

Senior Member
Messages
1,709
Location
Virginia, USA
I have been taking 5 mg of melatonin every night for many years now.

Wow, that's a nice amount! Maximum I can take (and do take) is 750mcg at night. More than that and I'm still feeling sleepy in the morning. Meanwhile, my mother takes 10mg and absolutely nothing happens to her.
 

Hip

Senior Member
Messages
17,808
Maximum I can take (and do take) is 750mcg at night. More than that and I'm still feeling sleepy in the morning.

That's interesting.

A quick Google check reveals that CYP1A2 is the main liver enzyme that metabolizes melatonin; perhaps some people have polymorphisms in their CYP1A2 gene that affects how quickly melatonin is removed from the body.

CYP1A2 is also responsible for most of the metabolism of caffeine.
 

BadBadBear

Senior Member
Messages
571
Location
Rocky Mountains
That's interesting.

A quick Google check reveals that CYP1A2 is the main liver enzyme that metabolizes melatonin; perhaps some people have polymorphisms in their CYP1A2 gene that affects how quickly melatonin is removed from the body.

CYP1A2 is also responsible for most of the metabolism of caffeine.

Interesting! I take slow release melo at 9 and it wears off around 2:30 or so. I can take 500 mcg of sublingual melo at that time (I don't take it after 4:30 am) and it wears off by morning. I wake around 6:15.

I am an 'ultra fast' caffeine metaboliser, maybe that's why I can take it close to wake up time.
 
Last edited:

Runner5

Senior Member
Messages
323
Location
PNW
Melatonin makes me start vomiting a few minutes after taking it. My Dad tried Melatonin and it did the same thing. Hmm, not that it adds to the discussion - just wanted everyone educated on my vomiting habits I guess ;-P haha
 

keenly

Senior Member
Messages
814
Location
UK
Yeah, why fake?
Two questions:
  1. Why is melatonin a fake supplement?
  2. Why is exogenous melatonin not a substitute for natural melatonin production?
Artificial equals fake, right?

Everyone should focus on circadian rhythm.

Am sunlight, then darkness at night will make your body produce melatonin. Supplements will not correct impaired circadian biology.
 

nanonug

Senior Member
Messages
1,709
Location
Virginia, USA
Artificial equals fake, right?

No.

Everyone should focus on circadian rhythm.

The focus of this thread is the protection of the electron transport chain, not circadian rhythm.

Am sunlight, then darkness at night will make your body produce melatonin. Supplements will not correct impaired circadian biology.

Prolonged-release formulation of melatonin (Circadin) for the treatment of insomnia

Abstract
INTRODUCTION:
Insomnia is common among the elderly. The use of hypnotic drugs in elderly patients is frequently criticized owing to dependency, cognitive impairments, falls and withdrawal effects. The production of melatonin, a physiological sleep and circadian rhythm regulator, declines with age. Prolonged-release melatonin (Circadin®), designed to mimic the endogenous pattern of melatonin production, is licensed for insomnia in patients aged ≥ 55 years.
AREAS COVERED:
This review summarizes published studies on Circadin's efficacy and safety (Summary of Product Characteristics and Medline search on 'Circadin' and 'insomnia').
EXPERT OPINION:
The main significant and clinically relevant benefits are improvements in sleep quality and latency, next-day morning alertness and quality of life. The responses may develop over several days. An oral 2-mg dose once daily, for 3 months, has generally been well tolerated with no rebound, withdrawal or 'hangover' effects and no safety concerns on concomitant therapy with antihypertensive, antidiabetic, lipid-lowering or anti-inflammatory drugs. Untoward effects of hypnotics on cognition, memory, postural stability and sleep structure are not seen with Circadin. Given as a first-line prescription, with 13 weeks' posology and the lack of rebound effects, Circadin has the potential to improve quality of life in insomnia patients aged 55 years and older and avoid long-term use of hypnotics.
 

BadBadBear

Senior Member
Messages
571
Location
Rocky Mountains
Artificial equals fake, right?

Everyone should focus on circadian rhythm.

Am sunlight, then darkness at night will make your body produce melatonin. Supplements will not correct impaired circadian biology.

I live on a farm and am outdoors every morning and evening. I get TONS of circadian entrainment every day regardless of the weather, probably more than many healthy people, and yet do not make optimal melatonin.

It would be ideal not to need it, but my body also does not make enough thyroid hormone, aldosterone, or progesterone any more, either. Thank goodness for supplements.
 

keenly

Senior Member
Messages
814
Location
UK
No.



The focus of this thread is the protection of the electron transport chain, not circadian rhythm.



Prolonged-release formulation of melatonin (Circadin) for the treatment of insomnia

Abstract
INTRODUCTION:
Insomnia is common among the elderly. The use of hypnotic drugs in elderly patients is frequently criticized owing to dependency, cognitive impairments, falls and withdrawal effects. The production of melatonin, a physiological sleep and circadian rhythm regulator, declines with age. Prolonged-release melatonin (Circadin®), designed to mimic the endogenous pattern of melatonin production, is licensed for insomnia in patients aged ≥ 55 years.
AREAS COVERED:
This review summarizes published studies on Circadin's efficacy and safety (Summary of Product Characteristics and Medline search on 'Circadin' and 'insomnia').
EXPERT OPINION:
The main significant and clinically relevant benefits are improvements in sleep quality and latency, next-day morning alertness and quality of life. The responses may develop over several days. An oral 2-mg dose once daily, for 3 months, has generally been well tolerated with no rebound, withdrawal or 'hangover' effects and no safety concerns on concomitant therapy with antihypertensive, antidiabetic, lipid-lowering or anti-inflammatory drugs. Untoward effects of hypnotics on cognition, memory, postural stability and sleep structure are not seen with Circadin. Given as a first-line prescription, with 13 weeks' posology and the lack of rebound effects, Circadin has the potential to improve quality of life in insomnia patients aged 55 years and older and avoid long-term use of hypnotics.

Clock Genes, Melanopsins, Melatonin, and Dopamine Key Enzymes and Their Modulation by Light and Glutamate in Chicken Embryonic Retinal Cells
http://sci-hub.cc/http://www.tandfonline.com/doi/abs/10.3109/07420528.2010.540685?journalCode=icbi20


Exogenous melatonin has been shown to thin the retina and it can suppress thyroid hormones and progesterone.It also impairs glucose tolerance am and pm...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173928/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4173928/

Many organs and systems can synthesize melatonin, of particular importance is its production in the skin and the eyes (organs designed to be exposed to light during the day and darkness at night) where light, specifically UV, excites tryptophan and eventually transforms it into melatonin. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227185/

Sleep disorders and abnormal circadian rhythms affecting the brain and other organs can worsen many pathologies involving aberrant dopamine neurotransmission, Güler said, including Parkinson's disease, depression, attention deficit/hyperactivity disorder, bipolar disorder, schizophrenia and drug addiction. https://medicalxpress.com/news/2017-08-neurons-brain-body-clock.html

Impact of oral melatonin on the electroretinogram cone response
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785757/
 

keenly

Senior Member
Messages
814
Location
UK
I live on a farm and am outdoors every morning and evening. I get TONS of circadian entrainment every day regardless of the weather, probably more than many healthy people, and yet do not make optimal melatonin.

It would be ideal not to need it, but my body also does not make enough thyroid hormone, aldosterone, or progesterone any more, either. Thank goodness for supplements.

Blue light at night? Have you tested your nnEMF levels?