Started at 1.5 and am at 4.5
I take it at 9pm
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@Paul you have given me inspiration to try LDN (coincidentally, newly offered by Healthspan). Better sleep, fewer bathroom visits at night, and other benefits seem like a good enough upside to give it a shot.
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@desertshores I just read your latest post on LDN (very negative) which seems contrary to the quote above. What happened? Iām asking because I am about to start on LDN.
I can only attribute the initial reaction to coincidence or a placebo effect.
After taking it for some time, I noticed a certain general malaise taking over, decreased energy, etc. There are just too many variables in the supplements that I am taking to be sure if something is working or not until some time has passed.
Of course, results may vary with LDN and I donāt think is a dangerous or bad thing to take.
If you want to give it a try do so. Many people have praised its virtues. It may be one of those love-it-or-hate-it supplements.
As an aside:
I donāt normally drink but after about two weeks of taking LDN I had a glass of wine with dinner and the wine tasted awful. It was later that I remembered that I was taking a substance normally prescribed for alcoholics and that is what probably accounted for the off taste with the wine.
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@desertshores Got it. Thanks for responding. I will give LDN a try, as I have done on so many things. I do worry about accumulating too many chemicals mixing around inside me at supra physiological doses. I was succeeding in reducing for a while, but now Iām accumulating again. I am going to think hard about this soon.
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LDN I have found, is when you find your sweet spot it works fine, maintains the energy boost but when you increase past your sweet spot it can have the opposite effect on energy, 1.5mg appears my sweet spot, I did titrate up to 3mg and started feeling quite lethargic, then I read on Fb group this can happen if you take more than you need, so I slowly reduced back down and found 1.5mg is good for meā¦
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Hi rivasp12:
Are you still using LDN on your patients? I am looking up long COVID treatment and saw this paper: Low-Dose Naltrexone use for the management of post-acute sequelae of COVID-19 | medRxiv
The Stanford ID group published a case series where they found LDN useful.
Where are you (or anybody else here) getting your LDN? Have you or anyone here used it for chronic fatigue/ POTS/ chronic pain syndrome/ long COVID?
Thanks.
PL
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You are absolutely right there is a sweet spot. The name āLow Dose Naltrexoneā mislead me. After all, we are taking doses much lower than the drugās prescribed dose for its primary intent.
I wasnāt paying attention when I ordered LDN. I order the 4.5mg dose and received capsules instead of the tablets I was expecting. It is harder to accurately adjust the dose with the capsule form. So this week I have been experimenting by opening the capsules and pouring some of the contents out.
~3mg before bed gave me a good extended deep sleep and I felt great the next day.
Last night I took 4.5 mg and I feel sleepy today with a queasy stomach.
To be honest when I read your first post about a sweet spot I was skeptical. Now I am a believer.
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Hi Paul
My team and I have used it on over 100 patients. Start at about 1.5 mg and titrate to 3.0 and then max of 4.5 mg. At these doses it may have cancer preventive properties, but may be cancer promoting,at least in theory, at higher dosing.
Weāve had success for chronic pain, MS, autoimmune issues, and even sweet craving control. Havenāt tried it for long Covid.
Itās easy for compounding pharmacies to custom make it for you.
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This is hot off the press from Cardiovascular Research Branch of NIH: https://twitter.com/EricTopol/status/1691173507869347841?s=20
"Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), named to reflect its āpostinfectiousā association, is a debilitating disorder characterized by exercise intolerance estimated to affect ~2.5 million individuals in the U.S. (1, 2). There are no clear abnor- malities by clinical testing to explain two prominent physical symptoms of ME/CFS, chronic fatigue and postexertional malaise, thus it is often a diagnosis of exclusion. 'The physical burdens of this disorder may also be accompanied by cognitive impairment, which further diminishes the patients quality of life. More recently, chronic fatigue has been associated with the post-COVID-19 syndrome (referred to as ālong COVIDā) and reported to bear resemblance to ME/CFS, raising the possibility that the pathophysiology of these two clinical entities may be related (3). Although the pathogenesis of ME/CFS has been extensively studied, no specific mediator molecule has been identified to explain the low aerobic capacity in this disorder. A number of ME/CFS studies have revealed redox imbalance and bioenergetic defects, both regulated by the mitochondria (4). Cardiopulmonary exercise testing of individuals with ME/CFS has shown decreased oxygen utilization and increased lactate accumula- tion, suggesting mitochondrial dysfunction (4-6). An important aspect of oxidative phosphorylation for ATP synthesis is the assembly of mitochondrial respiratory com- plexes into supercomplexes, which may reduce reactive oxygen species generation by facilitating the efficient transfer of electrons during respiration (7). Studies have shown that supercomplex formation in skeletal muscle is promoted by exercise and is positively correlated with mitochondrial oxygen consumption while metabolic dysfunction is associated with disruption of the supercomplexes (8, 9). During the clinical investigation of a patient with chronic fatigue, we found that WASF3, induced by ER stress, disrupts mitochondrial supercomplex formation and respiration by analyzing an aberrant sign- aling pathway observed in the patientās cells. Our study provides a molecular explanation for the patientās bioenergetic deficiency, which may be applicable to not only ME/CFS but also other conditions that feature chronic fatigue such as long COVID or rheumatic diseases associated with ER stress (10-12).
Significance Chronic fatigue is a debilitating symptom that affects many individuals, but its mechanism remains poorly understood. This study shows that endoplamic reticulum (ER) stress-induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance. Alleviating ER stress decreases WASF3 and restores mitochondrial function, indicating that WASF3 can impair skeletal muscle bioenergetics and may be targetable for treating fatigue symptoms."
An older paper (https://www.sciencedirect.com/science/article/abs/pii/S0304394006004502) showed that naltrexone can act through mitochondria. Therefore, it is possible that this may be related to the clinical observation that LDN can help ME/CFS and Long COVID via a pathway that is related to WASF3.
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Extremely interesting stuff Paul. Melatonin and ldn share some similarities. Melatonin also inhibits toll like receptors and is involved in mitochondrial health and function.
Of interest, WASF3 knockdown upregulates KISS1 in cancer cells which inhibits its invasiveness. Melatonin also upregulates KISS1. This could be a part of their anti cancer activity as well as the long Covid effects. https://www.cellmolbiol.org/index.php/CMB/article/download/2966/1435/6986
Iām wondering if a combination of ldn and melatonin might be synergistic.
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Iāve been pondering the high dose melatonin thing. Is it high dose at night, or melatonin all day long? Iāve used melatonin 0.3-3mg for sleep for 20 years, but have never used it during the day. I can imagine doing it on a highly active, outdoor day. But I canāt imagine sitting in my office with 30mg of melatonin in my blood. ZZZZZZZZZ.
I took melatonin for decades 1-10mg at night for a few months now I have been taking high doses at bedtime, typically 60 to 80mg, and another 10mg sublingually if I wake up during the night. Inspired by John Hemming and others in the thread: āMelatonin megadoses? - #46 by HigoMe33ā
It feels no different to me than taking 1mg doses. It does not cause me any daytime sleepiness. A little too much LDN does.
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For prevention, it seems that people are using 100 to 180 mg at night. Studies seem to suggest that itās safe . Melatonin, Beyond Sleep , is a pretty decent book by John Lieurance, written more for the lay person. Seems a little exaggerated, but still informative.
Better yet is the one by Russel Reiter called Melatonin. Heās one of the leading researchers in the field. It was also very informative.
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Thanks for the details. Iām tempted to try it. Maybe I wait to see what the LDN does first. (low low dose).
is there a US manufacturer/distributor making LDN? Just realized that you have to go to a compound pharmacy to get the low-dose Naltrexone which is a bit of hassle and compounding pharmacies could make mistakes. Did look into Ageless but the guy behind it had terrible reviews on the internet. Looks like itās all marketing people for his website too.
I use Gethealthspan.com who I believe gets it from a compounding pharmacy. I ordered it but havenāt received it yet.
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Got mine from India. See the list of trusted suppliers.
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FWIW
I have been using AgelessRx for LDN for the past 6 months. Posted about this on another thread on this forum.
Cost $100.00 for 3 month supply{at 4.5 mg per day dose] delivered with a prescription.
I have no financial interest in AgelessRx, I am a user of their service.
If you look online you can locate a $30.00 discount code for your first order.
Itās not a big deal. Start at 1.5 mg and work your way up. If it makes you groggy, go down. If youāre using it for pain relief and the effect wears off, stop for a while and restart. I do the same with gabapentin as well. Agree with BobinUK itās definitely about finding your personal sweet spot, probably based on weight, gender, age, and metabolism.
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