https://www.hh.um.es/Abstracts/Vol_40/40_5/40_5_745.htm
Summary. Background. Sarcopenia is a common age-related disease. Melatonin (MEL) is an age-related endocrine hormone, which displays a crucial role in resisting oxidative stress during aging. Importantly, the antioxidant properties of MEL can be mediated by mitochondria.
Objective. Therefore, we wondered whether MEL could mitigate oxidative stress caused by mitochondria in sarcopenia. Methods. The middle-aged mice were administered 5 mg/kg/d and 10 mg/kg/d of MEL for 2 months. Young mice were used as the control group.
Results. After treatment with MEL, the grip strength of the fore/hind limbs, running time, and distance were elevated, and the weights of the gastrocnemius (GA), tibialis anterior (TA), extensor digitorum longus (EDL), and soleus (SOL) were enhanced in middle-aged mice. Additionally, MEL was observed to alleviate histological damage and increase the cross-sectional area of muscle fibers in GA tissues of middle-aged mice. Furthermore, following MEL treatment, there was an increase in the percentage and size of normal mitochondria as well as mtDNA copy number but a reduction in the levels of malondialdehyde (MDA), protein carbonyl, and reactive oxygen species (ROS) in the GA tissues of middle-aged mice. At the molecular level, MEL repressed the levels of ATROGIN-1, muscle RING-finger protein-1 (MURF-1), and the ratio of p-P38/P38, but elevated the expression of cytochrome c oxidase subunit 4 (COX4), cystatin C (CYTC), nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), and peroxisome proliferator-activated receptor Ī³ coactivator-1Ī± (PGC-1Ī±) in the GA tissues of middle-aged mice. Importantly, 10 mg/kg MEL was more efficacious in the treatment of sarcopenia than 5 mg/kg MEL.
Conclusion. MEL attenuates sarcopenia in middle-aged mice, and the mechanism may relate to mitochondria-induced oxidative stress and the PGC-1Ī±/TFAM pathway. Histol Histopathol 40, 745-755 (2025)
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I just started higher dose melatonin. Looking forward to giving this a good go.
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Paiva
#3
What dose you considers āhighā ? I take 100-120mg througouth the nightā¦
There are people on this forum (myself included) who take over a gram a day. There are medics who think 3mg is high.
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Paiva
#5
Thanks John! There is a long way to go until we establish an accurate dosage that make sense for a long and healthy life! Until then, we are our own guinea pigsā¦
Iāve not got a milligram scale but I bought a 100g bag of pure melatonin and Iāve been having tip of teaspoon a few hours before bed for a couple of nights.
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Paiva
#7
Thanks! Please, let us know later how your experience goes with this dosage!
My view about melatonin is that it is most signficant when protecting mitochondrial DNA against damage, but that is probably also the hardest thing to measure. It has a lot of other effects as well.
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Interestingly when I first started taking melatonin I thought 10mg was a high dose and I would feel sleepy the next day. I seem to be handling these higher doses quite well considering. Itās certainly more than 100mg, possibly as high as 250mg.
It has a nice feel to it as well, certainly alters perception slightly. Puts me in a bit of a dream like state. I hear some people take high doses throughout the day as well to maintain high levels for health reasons.
One time I accidentally mixed up my night time and morning supplements up and took 10mg of melatonin before work, I felt like I was mildly drunk or stoned haha.
adssx
#10
3 Likes
Beth
#11
I wonāt bury the leadā¦ my question is, if I want to see if MEL helps my bones, how long would you guess I need to take it before it might show up in a DEXA? 6 months ish?
As someone who was just yelled at by their gyn for not being on fosamax, I appreciate these posts, and the dosage recommendations for humans.
Johnās trick of taking melatonin if I wake in the middle of the night works so well for me that I stopped taking it before bed, but that means Iām taking it many fewer nights because I often sleep through the night.
Iāll start taking 100mg before bed whether I need it or not.
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I would think citrate may be better for bone creation.
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Hi I live in Australia and would really like to try pure melatonin without fillers. Which brand do you use and how accessible is it? I saw a doctor last week who prescribed Voquily and the pharmacy compounders told me that they are no longer permitted to compound melatonin (this in Perth anyway) - that I must use the one prescribed. I looked at the fillers and no thans. Am taking NOW brand - have tried a few.
I got it off Pure Bulk. I just bought it.
I also have Life Extension IR/XR which combines instant release and extended release. This is good for sustained levels of melatonin, but itās very low dose. That was off iHerb.
Whether these get through customs is up to luck and the discretion of the customs officer who may come across it.
If you want something that is far less likely to be confiscated then you can find a domestic supplier, the websites Vitamin Grocer and Mega Vitamins have many brands available. But this isnāt pure melatonin without fillers, theyāre capsules, tablets or gummies.
Mega Vitamins has better brands available like Life Extension, Now and Swanson.
Iāve never tried prescribed melatonin, but I honestly canāt be bothered working through the system to get something so cheap and readily available.
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Its worth a try as I am really not keen on Voquily. I tried the Life Extension liquid version a while back (sickly sweet but it did work) the Now 3mg brand I have is rice flour. Doesnt feel right. I totally agree with you- only got prescribed because compounded seemed effective. I will look at the options you described thank you!
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Life Extension IR/XR also has filler ingredients but it is the only way I could find to get the āmicroactiveā form of melatonin which is extended release which has its own benefits, and was recommended to me by someone I respect.
Sounds like you might like the pure melatonin powder from Pure Bulk. Bulk Supplements is also an option.
You could capsule it yourself, or just use a spoon and dry scoop it like I have been. If youāve ever eaten any weird herbal/supplement powders before it wonāt be that bad. Itās slightly bitter, and the flavor lingers a bit. No big deal for me.
If you have a capsuling machine you could capsule some. If you have a milligram scale you could break one of the capsules open after filling them just to measure how much youāre getting on average per capsule if this is something you are interested in knowing. I am thinking of getting a scale soon.
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Thank you Travis.
I dont like alginate (the Life extension one) as it effects the thyroid amongst other things. Funny enough I have their sleep one with nobiletin though I havent tried it because it has colourants and other fillers. Though nobiletin is hard to find so maybe I could tonight. I did find their vanilla flavoured melatonin liquid to be effective a while back. Am defintely leaning towards pure - I would probably dissolve a small amt into my pomegranate juice. Have you had any side effects? I mean did it feel different to others?
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Iāve never heard of nobiletin, Iāll look into that one. Looks to be a component of citrus peels. Iām a big fan of orange peel powder, and citrus bergamot. I take these nightly. I wonder if I get nobiletin from these?
I personally just put the powder in my mouth and then down it with water. Funnily enough I downed it with some coffee a few days ago and had no lingering taste at all. I really should cut back on coffee lol!
I would recommend just putting it in your mouth, holding it there for a bit for some potential sublingual effects and then drinking it down with pomegranate juice (or whatever you want to drink it with.)
No side effects either, other than the fact that melatonin can leave you a big groggy the next day if youāre not used to it. My experience with melatonin, which I detailed in a previous comment, is that when you first start taking higher doses you can experience grogginess the next day. I used to not want to take the 10mg capsules the day before I need to wake up early for work. Iām just going to take this larger dose nightly now.
I feel no ill effects.
Iād advise slowly titrating upwards to gauge how you feel.
https://dergipark.org.tr/en/download/article-file/3392275#:~:text=In%20citrus%20fruits%2C%20nobiletin%20content,different%20geographical%20regions%20may%20vary.
Nobiletin was detected at a concentration of 0.43 mg/g in dried orange peels collected from California, whereas orange peels collected from China exhibited higher levels of nobiletin at 7.79 mg/g (4).
Discovery of Nobiletin from Citrus Peel as a Potent Inhibitor of Ī²-Amyloid Peptide Toxicity - PMC(2-(3%2C4,nobiletin%20on%20PC12%20cell%20models.
Nobiletin (2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxychromen-4-one) is one of the major polymethoxyflavones in the peel of citrus fruits, including oranges, mandarins, limes, and lemons [10]. Various pharmacological effects attributed to nobiletin include antioxidant, anti-inflammatory, anti-diabetic, anti-atherogenic and anti-carcinogenic activities [11,12,13,14,15]. The neuroprotective property of nobiletin has been demonstrated in several recent studies. The compound prevents ischemic brain injury by regulating the Akt/cAMP-response element-binding protein (CREP)/Bcl-2 pathway in SpragueāDawley rats. Nobiletin reduces AĪ²-stimulated memory impairment in several AD animal models, including olfactory bulbectomy mice, APP-SL 7ā5 Tg mice and 3XTg-AD mice [16,17,18].
There is some evidence showing that citrus peel may prevent AD.
Increasing evidence has demonstrated that amyloid-Ī² peptide (AĪ²), the hallmark of Alzheimerās disease (AD), evokes oxidative and inflammatory cascades, which ultimately lead to the death of neurons. The purpose of the present study is to demonstrate the effect of nobiletin, a representative compound of citrus peel, in preventive and therapeutic approaches against neuronal damage by exposure to AĪ²25ā35. Nobiletin significantly ameliorated AĪ²25ā35-mediated cell death by restoring abnormal changes in intracellular oxidative stress, cell cycle, nuclear morphology, and activity of apoptotic caspase.
Where do you get your citrus peel, please?
I tend to eat the whole slice of lemon/orange etc (perhaps cutting the harder part off the ends of a slice of lemon). Thatās because there seems reasonably good evidence that there are helpful things in the peel as long as it is well washed.
