I don't know what this Melatonin blurb is trying to say

[Bolt_Upright]

From this article: Antioxidants and Prooxidants: Effects on Health and Aging 2020 hindawi.com/journals/omcl/2...

This line: In addition, administration of melatonin to humans promoted reduction of COX-2 activity, nitrites and nitrates, and lipid peroxides that correlated with clinical improvement of PD patients [143]

The reference "143" is this document: [Effect of melatonin administration on cyclooxygenase-2 activity, serum levels of nitric oxide metabolites, lipoperoxides and glutathione peroxidase activity in patients with Parkinson’s disease] pubmed.ncbi.nlm.nih.gov/290... , which is a free article if you can speak Spanish: Efecto de la administración de melatonina sobre la actividad de la ciclooxigenasa-2, la concentración sérica de metabolitos del óxido nítrico, los lipoperóxidos y la actividad de la glutatión peroxidasa en pacientes con enfermedad de Parkinson gacetamedicademexico.com/fr...

Thoughts?

Here is the complete Melatonin section of the Antioxidant article:

3.1.1. Melatonin

A natural antioxidant capable of reducing cellular oxidative stress, melatonin protects mitochondrial functions in vitro. Low levels of melatonin were found in PD patients [135]. Zampol and Barros [136] prompted a study indicating that melatonin administration to cultured cells reversed α-synuclein damage to mitochondria. Additionally, Patki and Lau [137] investigated whether melatonin could reverse neurobehavioral deficits and mitochondrial disorders in an experimental model of PD, suggesting that, in the long term, melatonin protects not only mitochondria but also neurons in an animal model of chronic PD. Due to this factor, melatonin can potentially be effective in slowing the progression of idiopathic Parkinson’s disease and reducing oxidative stress and respiratory chain inhibition in other mitochondrial diseases. In a similar study, Paul et al. [138] identified that the administration of melatonin protects against behavioral deficits and loss of nigral dopamine and reduces oxidative stress by eliminating OH• radicals and boosting the activity of antioxidant enzymes in an animal model of PD. Similar results were observed by Li et al. [139] and Rasheed et al. [140]. Curiously, despite promoting the reversion of several rotenone- [141] and 6-OHDA-induced damage in rats [142], melatonin supplementation to animals was unable to improve locomotor activity. In addition, administration of melatonin to humans promoted reduction of COX-2 activity, nitrites and nitrates, and lipid peroxides that correlated with clinical improvement of PD patients [143]. Nevertheless, the association of melatonin with L-DOPA significantly decreased the side effects of L-DOPA therapy in mice [144]. A particular aspect of melatonin administration in PD lies on its effect on the occurrence of sleep disorders, a common finding in PD patients. In this regard, melatonin treatment promoted sleep improvement in animal studies [145–146], while its effect on clinical trials is controversial [147–149]. Notwithstanding, one meta-analysis study suggests melatonin therapy as highly indicated for the treatment of sleep disorders in PD patients [150].

[chartist]

A reduction in Cox-2 activity is considered anti inflammatory.

Nitrate via food is converted to nitrite which works to increase NO, NO2 and NO3 to perform positive biological functions, but nitrate/nitrite were formerly thought to mainly have unhealthy effects such as cancer, so not the most conclusive finding in this group.

Lipid Peroxides work to breakdown PUFAs/lipids through oxidative stress and a reduction would be considered positive for health.

Given the many many activities that melatonin has shown against PD, these three would hardly be the ones that I would consider to be in the top 10 activities promoted by melatonin toward improving the negative impacts of PD on the body, but these are what the study said correlated with clinical improvement of people with PD??? Correlation does not always equal cause and I would say that is an accurate statement in this case.

Art

[Bolt_Upright in reply to chartist]

Thanks Art! This is the abstract from the "Effect of melatonin administration on cyclooxygenase-2 activity, serum levels of nitric oxide metabolites, lipoperoxides and glutathione peroxidase activity in patients with Parkinson’s disease" article:

Objective: To determine the effect of melatonin (MEL) administration on ciclooxigenase 2 (COX-2) activity and serum concentration of nitric oxide metabolites, lipoperoxides and glutathione peroxidase (GPx) activity in patients with Parkinson's disease.

Methods: Prospective double-blind randomized clinical pilot trial. 13 patients were included and two groups were formed: MEL at doses of 25 mg orally every 12 hours for 12 months and placebo with corn starch. Patients were assessed using the Unified Parkinson's Disease Scale. A blood sample was taken at baseline and every 3 months until 12 months.

Results: COX-2 activity decreased as did nitrates/nitrites (3, 6 and 9 months) and lipoperoxides (9 and 12 months); GPx exhibited no significant differences.

Keywords: 4-OH-alkenes; Ciclooxigenase 2; Glutathione peroxidase; Malon-dialdehyde; Nitrates/nitrites; Parkinson.

Maybe this has confusing wording because the original was in Spanish? The first sentence is about melatonin not improving locomotor activity, then they start the next sentence with "In addition", which leads your mind into thinking they are adding some more bad news, when in fact they are giving positive news?

"Curiously, despite promoting the reversion of several rotenone- [141] and 6-OHDA-induced damage in rats [142], melatonin supplementation to animals was unable to improve locomotor activity. In addition, administration of melatonin to humans promoted reduction of COX-2 activity, nitrites and nitrates, and lipid peroxides that correlated with clinical improvement of PD patients [143]."

[chartist in reply to Bolt_Upright]

It seems strange to me that these were the parameters that they were concentrating on given the many other effects that melatonin has shown in people with PD. I think it would be a much more important feature of melatonin that at higher dosing it has returned oxidative stress parameters to a level very similar to healthy controls or that it crosses the blood brain barrier or that it has anti inflammatory qualities or that it has shown to protect dopaminergic neurons in animal models. The mitochondria protective effects are priceless. The fact that it can modulate autophagy and mitophagy as needed to promote health would also be an important consideration. Another very important consideration is that it can treat or prevent cardiovascular disease which is at elevated levels in PwP. I would think this last feature would be worth the price of admission all by itself, but I don't think I have ever seen a PD study that even highlighted this point.

A 180 mg study at this point seems entirely relevant to PD given the known safety profile of melatonin, imo. They did that one year 600 mg/day study for benfotiamine and AD, is it too much to ask for a 180 mg/day melatonin study for a year in people with PD?

Art

[Little_apple]

Did they mean to say which correlated ? That correlates is confusing

line: In addition, administration of melatonin to humans promoted reduction of COX-2 activity, nitrites and nitrates, and lipid peroxides that correlated with clinical improvement of PD patients [143]

[goldengrove]

I don't speak Spanish but yes, Bolt, I suspect the problem is with the inappropriate translation of linking phrases like "In addition". The sentence about melatonin promoting the reduction - i.e. decreasing - COX-2 activity supports melatonin as an anti-inflammatory agent, certainly a benefit. I'd like to be able to read the article to see how significant the improvement in PD was. Only a small study, unlikely to be powered to show statistical significance, but it was placebo-controlled.