#465

Comparing Extracellular and Intracellular Antioxidants in Human Sperm Rapid Freezing: Hypotaurine Versus Melatonin 2025

Results: The HYP group exhibited higher normal morphology (p < 0.001), viability (p < 0.001), and higher acrosome integrity (p < 0.001) and lower DNA fragmentation index (DFI) (p < 0.001) than the C and MEL groups. No significant difference was observed in the total and progressive motility percentage among the antioxidant and frozen control groups. The MEL group had a significantly higher level of HspA2 mRNA compared with F and C groups (p < 0.05). The expression of Caspase9 was unaffected by including MEL and HYP in all experimental groups.

Elevated HspA2 = improved sperm maturation, acrosome function and fertilization potential?

#466

Here are the four types that I currently use. The most recent time I awoke with a headache I used the 5 mg dissolving tabs and a 60 mg pill. I have had headaches with several combinations, I suspect from taking a higher dose than I am used to.

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#467

Yes, that sounds like a good option for next time I have to buy. While there probably are some unwanted impurities or added colors/flavors, etc in my supplements, I figure that there is some mechanism that drives both the propensity to get headaches and prevent headaches with melatonin itself. Can’t wait to learn what it is.

1 Like
#468

Association Between Melatonin Receptor Agonists and Cardiac Arrhythmia; Disproportionality Analysis Studies Using Pharmacovigilance Databases 2025

Among the drugs used for insomnia, the use of benzodiazepine and non-benzodiazepine hypnotics is correlated to the occurrence of cardiac arrhythmia. Conversely, melatonin receptor agonists may exert cardioprotective effects. Therefore, in the present study, we investigated the association between the use of melatonin receptor agonists and the occurrence of cardiac arrhythmia using the Food and Drug Administration Adverse Event Reporting System (FAERS). Eligible patients are registered in FAERS. The targeted drugs were melatonin receptor agonists and benzodiazepine receptor agonists (BZRAs). The target disease was cardiac arrhythmia, and data for the disease were extracted from the Medical Dictionary for Regulatory Activities (MedDRA) 27.1; Standardized MedDRA Query (SMQ). The reporting odds ratio (ROR) was calculated in the study. The results showed that melatonin receptor agonists were negatively correlated with all cardiac arrhythmia-related SMQs. The RORs for each SMQ were as follows: “cardiac arrhythmias” (ROR: 0.47, 95%CI: 0.41–0.54), “bradyarrhythmias” (ROR: 0.20, 95%CI: 0.10–0.40), “tachyarrhythmias” (ROR: 0.21, 95%CI: 0.13–0.33), “supraventricular tachyarrhythmias” (ROR: 0.24, 95%CI: 0.14–0.41), “ventricular tachyarrhythmias” (ROR: 0.05, 95%CI: 0.01–0.33), and “TdP” (ROR: 0.32, 95%CI: 0.25–0.41). Conversely, BZRAs were positively correlated with cardiac arrhythmia-related SMQs. Overall, the present results suggest that compared with BZRAs, melatonin receptor agonist usage is weakly associated with cardiac arrhythmia.

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Melatonin and melatonin-receptor agonists both activate MT1 and MT2, so could melatonin as well be cardioprotective?

3 Likes
#469

Still more benefits from melatonin.

New to me: Myeloperoxidase (MPO) as a Biomarker. I learnt this from watching a new YouTube video from Nick Norwitz, MD, Phd.

“Myeloperoxidase (MPO) as a Biomarker:
Elevated MPO levels in the blood are increasingly recognized as a biomarker of inflammation and oxidative stress, particularly in cardiovascular risk assessment.”

"In summary, MPO is a double-edged sword of the immune system, crucial for defense but capable of causing significant damage. Melatonin, through its potent antioxidant and anti-inflammatory properties, appears to be a natural guardian against the harmful aspects of MPO activity, highlighting its broader protective roles in health and disease beyond just sleep"

"Melatonin Prevents Myeloperoxidase Heme Destruction and the Generation of Free Iron Mediated by Self-Generated Hypochlorous Acid - PMC.

https://www.ahajournals.org/doi/10.1161/hypertensionaha.110.158170#:~:text=Galijasevic%20S%2C%20Abdulhamid%20I%2C%20Abu,%3B%2047%3A%202668–2677.

https://www.youtube.com/watch?v=inTK-9DCxf0"

4 Likes
#470

What’s the highest you tried @LukeMV?

#471

All recent articles on melatonin focus on fertility for whatever reason. This one is from Egypt, so not of the highest quality: Melatonin as a potential adjuvant to mitigate depakine‑induced testicular damage in rats through its biological features 2025

Moreover, reactive oxygen species and malondialdehyde formation were decreased in the testis compared to the depakine-treated rats, indicating improvement in the redox status in the testis. The improvement of redox balance caused a remarkable regression of apoptotic regulating proteins (Bax, Bcl-2, and caspase-3) in the testis and downregulated inflammatory cytokines and chemokines (NF-κB, TNF-α, IL-6, ICAM-1, and MCP-1), indicating protection of spermatogenic cell viability.
The combination treatment with MLT and depakine sustained male reproductive status, which can be attributable to the integrated antioxidant, anti-inflammatory, and antiapoptotic properties of MLT.

#472

Behavioral and Metabolomics Analyses of Drosophila melanogaster with Chronobiotic Melatonin Treatment: Effects on Locomotor Activity, Circadian Integrity, and Metabolic Pathways 2025

We found that 1 mM and 4 mM melatonin doses significantly increased Drosophila locomotor activity. Melatonin at a high concentration (4 mM) exhibited a protective effect to reduce mortality in Drosophila.
We discovered 20 biologically relevant metabolites altered by melatonin, including key perturbations in arginine biosynthesis, alanine/aspartate/glutamate metabolism, and pyrimidine pathways. Notably, melatonin upregulated glutamine, a potential indicator of enhanced neurotransmitter synthesis and broadly modulated amino acid and nucleotide metabolism, suggesting dual roles in neuroprotection and energy homeostasis.

@John_Hemming, according to ChatGPT, these doses are equivalent to about 50 mg/day (1 mM) and 200 mg/day for an 80 kg adult: ChatGPT - Melatonin Dose Conversion

2 Likes
#473

One uncertain issue that I may aim to resolve is the pharmacodynamics of doses over 1g of melatonin in Homo Sapiens. There is a multicompartmental approach as melatonin can get everywhere quite quickly. Hence the usual half life does not necessarily apply.

To partially resolve this I would need to take a large dose of melatonin then measure serum every half hour or so.

2 Likes
#474

Only 10mg, which I did for maybe a year straight quite some time ago. I haven’t done the super high doses being discussed here.

#475

Yes 10 is inferior to 2: Melatonin megadoses? - #316 by adssx

I wonder if even higher doses could be better.

1 Like
#476

John -

Just nice to have you around leading on so many fronts.
Much appreciated.
Many thanks.

A

2 Likes
#477

I tried a megadose again last night. Fell asleep really good, but woke up way too early feeling awake.

1 Like
#478

Try taking it 3 hours before bed

2 Likes
#479

I was looking to add products to my melatonin ‘wardrobe’ last night, and while finding a Solaray brand melatonin that also contains glycine, I noticed they have another option that contains ‘Somato’. It’s melatonin from tomatoes, sourced from Nutraland.

I’ve heard Solaray is a high quality brand, thus I’m intrigued. Google says it works as well and there is potential for it to be absorbed better (I doubt it but who knows).

Any thoughts on if this might have any advantages?

Perhaps it’s just a brilliant way to sell melatonin in markets where melatonin is not allowed, as this is a food

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Their 10mg melatonin option with glycine (not the Somato) is extended release. That seems interesting, but then I got paralysis by analysis due to the fact I take taurine at night and many people say don’t take glycine within 4 hours of taurine. Anyone have thoughts on this one?

2 Likes
#480

I’m not sure about the glycine and taurine issue but I have taken that formula before and really liked it. I may go back to it when I need to reorder.
Edit: the 10mg extended release version with glycine.

1 Like
#481

I know you can get natural melatonin from tart cherry. I experimented with tart cherry juice and honestly it made me quite sleepy. I’ve got a bottle of carbonated grape/cherry juice in the fridge I’m looking forward to cracking open.

Keep us updated with this tomato melatonin, I’ve never heard of it.

1 Like
#482

Melatonin Ameliorates Zearalenone-Induced Ovarian Damage in Mice through Antioxidative Effects 2025

:warning: Preprint :warning:

Zearalenone (ZEN) is a mycotoxin synthesized by fungi of the Fusarium genus, frequently identified in contaminated grains, foodstuffs, and animal-derived products. Its estrogenic activity perturbs endocrine homeostasis, resulting in reproductive dysfunction in female animals. Oxidative stress is implicated in DNA damage, notably double-strand breaks (DSBs). The Ataxia-Telangiectasia Mutated (ATM) protein serves as a pivotal regulator of the DNA damage response (DDR). Upon the occurrence of DSBs, the ATM-Chk2-p53 signaling cascade is activated, triggering mechanisms such as DNA repair, cell cycle arrest, apoptosis, or senescence. Melatonin (MT), an endogenous antioxidant, facilitates the development of oocytes and granulosa cells by scavenging reactive oxygen species, regulating the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), modulating estradiol (E2) levels, and mitigating oxidative stress. This study examined the deleterious effects of ZEN on mouse ovarian tissue and granulosa cells (GRM02) and investigated the potential ameliorative role of MT in counteracting ZEN-induced oxidative stress, thereby enhancing ovarian function and diminishing cellular damage. Furthermore, the study investigated the involvement of the ATM-Chk2-p53 pathway in the protective mechanism of melatonin (MT). The results elucidate the reproductive toxicity of zearalenone (ZEN) and offer a theoretical foundation for the application of MT as a protective feed additive.

#483

i doubt you’d get high amounts, maybe if you consume 10kg of tart cherries lol

#484

I think the figures are around 13 nanograms per gram. (for those who don’t know SI milli,micro,nano,pico) so 13 1,000,000,000 th of a gram in a gram.