Cyfrin
#290
I follow the work of Doris Loh here is a link to her
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Bicep
#291
Wow, it looks like I should buy a bag of melatonin just in case. Crazy high dosage. I take 36 every night and thought that was a lot.
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Cyfrin
#292
My health protocol is so extensive that it is hard to be sure of exact changes. I can say it increased my energy and made my periods more regular.
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Repairing DNA Damage: Scientists Identify New Benefits of Melatonin Supplementation
Researchers say that larger studies examining varying doses and long-term effects are now warranted.
A small clinical trial, published in Occupational & Environmental Medicine, suggests that melatonin supplementation may help counteract DNA damage linked to night shift work by enhancing the body’s ability to repair it.
The researchers emphasize the need for larger studies to explore different dosages and assess the potential long-term effects of melatonin supplementation.
Night shift workers experience suppressed nighttime production of melatonin, a key hormone regulating the body’s internal clock. This suppression weakens the body’s ability to repair oxidative DNA damage—a natural byproduct of cellular processes—potentially increasing the risk of certain cancers.
To investigate whether melatonin supplementation could mitigate this damage by improving DNA repair, the researchers conducted a study involving 40 night shift workers.
https://scitechdaily.com/repairing-dna-damage-scientists-identify-new-benefits-of-melatonin-supplementation/
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Once this is properly researched and sufficient priority is given to brain cell protection rather than minimising the exposure of other cells to melatonin I will be surprised if the recommended dosage is under 100mg per night.
Getting to this point, however, may take 10-30 years as there is no money to be made here and Trump’s team have decided to shut down a lot of US research. (regardless as to what is being researched).
I have, however, cited the papers with measurements of CSF melatonin levels which are the levels that anyone who wishes to protect their brain cells should be aware of.
5 Likes
adssx
#295
Paper: Melatonin supplementation and oxidative DNA damage repair capacity among night shift workers: a randomised placebo-controlled trial 2025
In a 1-month randomised placebo-controlled trial, we demonstrated that consumption of a 3 mg melatonin supplement before engaging in daytime sleep improved the ability of night shift workers to repair oxidative DNA damage. No previous trials of melatonin supplementation and oxidative DNA damage have been conducted.
A dose of 3 mg of melatonin was selected for the study because it would likely produce physiological to supraphysiological levels of circulating melatonin in most people even after accounting for interindividual variation in bioavailability of melatonin.
Large interindividual variation in bioavailability of exogenous melatonin poses a challenge to identifying ideal doses of melatonin supplements for intervention/treatment.
In addition, previous research has demonstrated that even high doses of melatonin do not tend to produce sedative effects.
Given the limited scope of the trial, we were unable to evaluate multiple doses of melatonin supplements, nor were we able to evaluate the long-term efficacy of melatonin supplementation.
Our randomised placebo-controlled trial suggested melatonin supplementation may improve oxidative DNA damage repair capacity among night shift workers. Our findings warrant larger-scale trials considering multiple doses of melatonin, interindividual variability in melatonin bioavailability, and the impacts of long-term use of supplements. Assessing long-term efficacy is critical since those who work night shifts for many years would need to consistently consume melatonin supplements over that time frame to maximise the potential cancer prevention benefits.
Melatonin also extends lifespan in animal models: Melatonin and its possible anti-ageing properties
Not tested in the ITP though.
3 Likes
adssx
#296
@John_Hemming: is there an easy way to measure creatinine-adjusted 8-hydroxy-2′-deoxyguanosine (8-OH-dG)?
The Exposure Biology and Analytical Chemistry Laboratory at Duke University used high pressure liquid chromatography-tandem mass spectrometry to measure 8-OH-dG and 6-sulfatoxymelatonin (aMT6s), a marker of circulating melatonin levels, in each urine sample.18 19 A second set of urine samples from a randomly selected 10% of participants were dispersed among study samples as blind duplicates. Values below the limit of detection (LOD) were replaced with LOD/√2.20 Creatinine was measured in the urine samples with the Creatinine Colorimetric Assay Kit (Cayman Chemical) and a microplate reader. Concentrations of 8-OH-dG and aMT6s were creatinine adjusted for all analyses and expressed as ng/mg-creatinine concentrations.
This would allow us to see the benefits of various doses from 1 mg to 1,000 mg.
adssx
#297
Interesting ongoing trials:
- Disease Modifying Potential of 5mg of Melatonin on Cognition and Brain Health in Aging (NCT03954899): “The study will examine whether 5mg melatonin (over the counter, OTC) over a 9-month period improves Alzheimer’s disease (AD) biomarkers and cognitive function in two groups of individuals: those with mild cognitive impairment (MCI+) and those who are not (MCI-).” Results in 2026
- Effects of 3-Month Melatonin Treatment on Regional Cerebellar Structure and Blood Biomarkers in Alzheimer’s Disease Spectrum (NCT06756828): 2 mg, results in 2027.
- Oral Bedtime Melatonin in Critically Ill Patients (Mel-ICU) (NCT06156059): 100 mg daily, results in 2027.
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The problem testing endogenous metabolites is that unless the concentration shifts by a material amount the outcomes wont shift by a material amount.
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adssx
#299
And yet the 3 mg study found significant improvement in DNA damage! (But in a particular population that might have low baseline levels)
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True. In the end each molecule of ROS can only be reduced once (as a rule). Melatonin starts with the ability to reduce 9-10 molecules of ROS. If there is not enough melatonin for all the ROS then additional melatonin helps. There question in the end is how much damage the ROS does because it is not caught by melatonin.
At a point, however, adding melatonin will not do that much.
2 Likes
Several urine tests available on Rupa test this. DUTCH and GDX Metabolomix+ to name two. It’s interesting that night shift workers have elevated 8-OH-dG. Personally I have elevated F2-isoprostane (another marker of oxidative stress) but my 8-OH-dG is normal.
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Strange, they state that 8-OH-dG increases with melatonin supplementation. AIUI, we want 8-OH-dG to be low as it is an indication of oxidative stress damaging DNA. What am I missing here?
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Nlo
#303
What time do you think it’s best to take the higher doses?
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The night shift workers with a certain Melatonin MT2 receptor mutation are especially prone to night-shift related problems and increased risk of Alzheimer’s disease.
The same mutation increases risk of dementia in people older than 85 yo.
Both groups have a lower baseline melatonin levels.
I tried to find any information about using higher doses of Melatonin for prevention of dementia in this population, but unsuccessfully.
3 Likes
Tim
#306
If I take a sub-milligram dose, I feel hung over the next day. If I took a massive dose, the hangover could be equally as massive.
1 Like
adssx
#307
Per ChatGPT (I have no idea whether this is correct or not):
In most contexts, a high level of 8-OH-dG in tissue might indicate that there’s significant oxidative damage. However, when we measure urinary 8-OH-dG, we’re actually capturing a by‐product of the DNA repair process. When DNA damage occurs, cells use repair mechanisms—specifically, the base excision repair pathway—to excise damaged bases like 8-OH-dG from the DNA. Once excised, these modified bases are excreted in the urine.
Increased urinary 8-OH-dG excretion during daytime sleep (with melatonin) suggests that the repair process is more active. Melatonin appears to boost the repair machinery, leading to the removal and subsequent excretion of more oxidized bases.
Conversely, if repair were impaired, the damaged bases might remain in the DNA rather than being excreted, resulting in lower urinary levels even though the cellular damage is higher.
Thus, while you might intuitively think “less 8-OH-dG is better” because it signifies less damage, in this study, higher urinary 8-OH-dG actually indicates that the body is effectively repairing and clearing oxidative damage. Essentially, the assay is using 8-OH-dG excretion as a surrogate for repair capacity rather than a direct measure of oxidative stress burden.
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I guess that could make sense? Alternatively, daytime melatonin is causing dna damage that requires more repair. The study also only showed relatively minor increases on an absolute level. The medians were very low indication of dna damage and the post-melatonin was still low.
adssx
#309
What I’m not sure to understand is: is there an absolute measure of DNA damage? In the study they measured repair. If repair increases it could be due to increased damage or increased repair capacity.
If metformin both prevents future damage and improve current repair capacity then:
- Which dose (if any) maximizes damage prevention?
- Which dose (if any) maximizes repair capacity?
If there’s such a threshold and you reach it then theoretically the urinary metric could reach 0 after some point as their would be no more damage (prevention + previous repair).
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Yea this is why the study is a bit confusing to me. 8-OH-dG in the contexts I’ve seen it used is typically a measurement of dna damage (ie you have increased repair due to increased damage). So interventions looking to reduce dna damage would seek to reduce this value. I would also suspect that in the opposite case you would want to see this value reduced in the long term. If your intervention is trying to increase dna repair, initially 8-OH-dG should increase until enough repair has been done to overcome the ongoing/cumulative damage, and then 8-OH-dG should decrease.
In the context of melatonin, given that it’s a potent antioxidant, I would have expected that it would fall under the former - reduction of damage, and we’d see a decrease in 8-OH-dG.
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