Melatonin and the electron transport chain

[BadBadBear]

Melatonin drug use in complex treatment of hypothyroidism manifest

http://www.endocrine-abstracts.org/ea/0026/ea0026p394.htm

"Conclusion: The inclusion of melatonin in the standard therapy for symptomatic hypothyroidism showed that the drug can affect the pituitary–thyroid system, removing anxiety and depression."

BTW I googled 'is melatonin bad for your thyroid' and this plus a couple other studies which cast a favorable light on exogenous melatonin supplementation came up. Would be interested to see studies showing otherwise (not interested in genetically engineered mice and chicken embryos).

 

[nsdn]

I have been taking 5 mg of melatonin every night for many years now.

It does not deepen sleep or make sleep more restful, but I find it helps me get to sleep more quickly. I also find melatonin when taken at a regular time at night helps prevent the sleep inversion that many ME/CFS patients get, see this thread:

Sleep Cycle Inversion (Awake At Night, Sleeping During Day): A Simple Technique Fixed This For Me.

Do you try 0,3 mg? See this: https://academic.oup.com/jcem/article/86/10/4727/2849013

 

[Hip]

Do you try 0,3 mg?

Interesting. I will have to try a lower dose as an experiment; but I think the last time I tried to reduce the dose, I lost the benefits.

 

[pamojja]

Do you try 0,3 mg? See this: https://academic.oup.com/jcem/article/86/10/4727/2849013

Exclusion criteria consisted of major psychiatric diagnosis on Axis I of DSM IV; regular use (once a week or more) of hypnotics, melatonin, stimulants, or other medications that may affect melatonin levels (e.g. β blockers, drugs that affect prostaglandin synthesis, or drugs that activate hepatic melatonin metabolism) and unwillingness or inability to discontinue the occasional use of these medications for at least 4 wk before beginning the protocol; acute or unstable chronic conditions, including but not limited to insulin-dependent diabetes, uncontrolled thyroid disease, kidney, prostate, or bladder conditions causing excessively frequent urination (more than three times per night), congestive heart failure, angina, other severe cardiovascular disorders, hepatitis, asthma or severe respiratory allergies, stroke, cancer if less than 1 yr since end of treatment, conditions associated with chronic pain such as fibromyalgia, and neurological disorders such as Parkinson’s disease, Alzheimer’s disease, and epilepsy; more than“ moderate” alcohol use, as defined by the Quantity-Frequency-Variability Index; unwillingness or inability to maintain a regular sleep/wake cycle during the entire period of the study; sleep apnea/hypopnea index >10;

The problem with all studies as this is, that the didn't study someone with multiples of chronic conditions like me. I tried 0.3 mg and gradually increased where I got the most benefits.

 

[pattismith]

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.

I tryed 1.8 mg yesterday night and got headache not long after and still in the morning, and I am feeling very cold today.

This dose is far too much for me!

 

[pattismith]

(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.

I have not digged more in this review, but it seems to say that on the contrary melatonin is inhibiting OXPHOS.

I was looking for papers talking about melatonine effects on ions currents, because I think it is the main reason why I can't tolerate this drug.
I took it 19 hours ago, and I am just starting to recover from the intake.

Pharmacological Actions of Melatonin in Acute and Chronic Inflammation
February 2002

A vast number of experimental and clinical studies implicates oxygen-derived free radicals (especially, superoxide and the hydroxyl radical) and high energy oxidants (such as peroxynitrite) as mediators of acute and chronic inflammation.
The purpose of this review is to summarize the pharmacological actions of melatonin in acute and chronic inflammation.
Reactive oxygen species can modulate a wide range of toxic oxidative reactions.

These include initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane sodium / potassium ATPase activity, inactivation of membrane sodium channels, and other oxidative modifications of proteins.

Reactive oxygen species (e.g., superoxide, peroxynitrite, hydrogen peroxide and hydroxyl radical) are all potential reactants capable of initiating DNA single strand breakage, with subsequent activation of the nuclear enzyme poly (ADP ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death.
These toxic reactions are likely to play a role in the pathophysiology of inflammation.
Melatonin has been shown to possess both in vitro and in vivo important antioxidant activities as well as to inhibit the activation of poly (ADP ribose) synthetase. A large number of experimental studies have documented that melatonin exerts important anti-inflammatory actions.

 

[nanonug]

I took it 19 hours ago, and I am just starting to recover from the intake.

You took too much melatonin. For me, 1mg is my absolute maximum but I still only choose to take 0.75mg in sustained release (6 hours) formulation.

Reactive oxygen species can modulate a wide range of toxic oxidative reactions.
These include initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane sodium / potassium ATPase activity, inactivation of membrane sodium channels, and other oxidative modifications of proteins.

Unless I'm reading this wrong, it seems to me they are talking about ROS, not melatonin.

 

[pattismith]

You took too much melatonin. For me, 1mg is my absolute maximum but I still only choose to take 0.75mg in sustained release (6 hours) formulation.
Unless I'm reading this wrong, it seems to me they are talking about ROS, not melatonin.

Oh yes, thank you nannonug, my headache makes my brain jumping and missing sentences.

Of course you are right, melatonin protects against ROS, so it protects against Oxphos inhibition, that's fine!

On the other hand I have read other papers where they said melatonin have an effect on ion channels, and I am very sensitive to this ... so if I try it again, I will take only a very tiny dose, maybe 0.2 mg .

I had a very bad day, I was very cold, vivid dreams, headache...I don't want to experience it again!