Anyone actually experience marked increased energy from NMN?

Sebastian Gastrointestinal discomfort has been reported.

Negative Effects of Resveratrol | Livestrong.com

Michael 

I stopped NMN and Resveratrol and the symptoms disappeared. Started Resveratrol again. No symptoms. Started with half a dose NMN : No symptoms. Took 1g of NMN : Same symptoms as before . Upset stomach and diarrhea. So now I started to take the NMN AFTER breakfast (No fasting stomach) and the promblems seem to have disappeared. Now I don’t know how important it is to take the NMN on a fasting stomach but taking it after breakfast is working for me. Cheers 

JH How are you getting Rapamycin? Doctor prescribe it?

John Ramos buy from India, no prescription needed. https://www.rapamycin.news/t/importing-rapamycin-to-save-money-pt-2/82

JH Did you have to fill out paperwork? Is it really a firedrill? LOL Or can you go to a known good website and order? 

John Ramos No paperwork, just go to www.indiamart.com and choose a vender, i have good experience with Niba Healthcare vender, use wise.com to transfer fund.

JH Hi much did you buy and how much are you taking? Is 3mg the dose?

John Ramos Biocon Rapacan 1mg costs about $1, Zydus Siromus about $1.5.

i take 6mg weekly or 3mg weekly with grapefruit juice.

Bart Balder  Thank you for reporting agitation when taking NMN. I will be observant, this since I am considering supplementing with NMN. I have had similar experiences with Q10 and Vitamin K1. They make me agitated and I want to avoid taking supplements that have that effect on me.

Karl there are liposomal NR and liposomal NMN available in the market, you may try them if it works.

JH The guy from Modern Healthspan posted a video in which he said he saw raised levels of NMN in the blood from liposomonal NMN https://www.youtube.com/watch?v=NcFhJHHGGEI&t=2s

But, being in the blood doesn't show that it moves into the cells.  It's a fairly large molecule & would need to be moved in via active transport, both to the cell itself & to the mitochondria.

Does anyone have any info on how well NMN is transported across cell membranes?

JH According to tests available from DoNotAge and Alive by Science(ABS), just NMN does raise NAD+, you can get your dose right by taking one of the tests. Richard of Modern Healthspan did it in one(some) of his videos. I had kind of a pissy run in with a rep from Alive by science so I'm going to stick to DoNotAge or Prohealth with both sell the same NMN. My last batch of NMN from ABS was very different, told them that and they got pissy....

Jack Black You can look it up but the dosing is about 2g/day(I take) for CA-AKG or AKG, according to "The Skeeky Science Show" it the AKG that does the magic at least what I take. I wouldn't take Nicotinamide, useless. Doesn't do anything for NAD+ production.

Jack Black rapamycin, I wouldn't go for any of the Chinese suppliers unless you done business with them before. Here's info from another member "just go to www.indiamart.com and choose a vender, i have good experience with Niba Healthcare vender, use wise.com to transfer funds.

AKG, yes, I bought CA-AKG but it appears it's just the AKG, watch this short video.

https://youtu.be/FOQzxbmfVa8

Amazon... Nutricost Arginine AKG Powder 300 Grams (AAKG) - 3G Per Serving & 100 Servings - Pure Arginine Alpha Ketoglutarate

John

John Ramos Hey John, I got my Rapa from Indiamart and also theantiaging.store So far so good. Too early to spot any differences. AKG seems to be the thing that gave me extra energy when I'm exercising. I have ca-akg in only 300mg tabs, quite expensive, then Creatine-AKG in 1g tabs which was much more reasonable. The reason I avoid Arginine supplements is that this amino acid is used by the herpes virus to replicate. Though I don't have herpes per se, everyone has it somehow e.g. chickenpox so I am being cautious. 

Jack Black  Exactly. The possible side effects of arginine are something I would prefer to avoid. Never heard of Creatine-AKG...that sounds very good. Where do you obtain yours? And rapa is now pretty reasonable, especially if you use the grapefruit protocol.

chuck stanley My Creatine AKG came from Vitafy.ch

https://www.vitafy.ch/creatin-akg-180-kapseln.html?utm_source=parcellab&utm_medium=email&utm_content=any&utm_campaign=any&utm_term=any

Jack Black now if I could only find it in the U.S. 

Jack Black The "theantiaging.store" for Rapa is expensive, you think you're getting enough bang for the buck? How much is it from India?

I'm taking 2g of CA-AKG because i have it and that is supposed to be the dose.

Speaking of Chickenpox, did you get the shingles vaccine? Don't know why you would get herpes...maybe a private thing?

John

John Ramos https://en.wikipedia.org/wiki/Herpesviridae Chickenpox is a herpes virus, not a private matter at all. You're clearly asking me if I have the genital version, which I can happily deny.

My concern with buying Rapa is getting something with the actual molecule and not fake stuff. The Indiamart stuff was slightly cheaper, exact price I don't remember.

I'm also concerned about the chinese market for goods. Very much a buyer beware environment. As such I've ordered a bunch of Ca-AKG from DoNotAge using the Dr Brad Stansfield discount code. Expensive again, but cheaper per gram than Kirkman. 

Jack Black Jack, the only thing I know about Chickenpox is about shingles. I got the vaccine because I had chickenpox as a kid and had one episode of shingles, I didn't even know it is/was a herpes virus.

I suspect that the "theantiaging.store" is also a Indian enterprise, their Rapa is Made in India. To my way of thinking, I question is if anybody is getting enough bang for the buck. 

I'm concerned about the Chinese market also, I have one I have purchased from since 2015, provides COA's, HPLC's and whatever else you want. They go to all the international shows and send me invites.

I don't buy anything other than NMN from DoNotAge and Prohealth, they sell the same product, Uthever(Youth Ever). I don't like the NMN from AliveByScience, it was changed(clumpy and didn't mix right) and a salesperson tried to tell me it was the same...

Jared has had no effect on my epigenetic age

Jared I notice Ca-AKG when I exercise. You call for the energy and it's there. In domestic life where I'm not needing the energy boost I don't notice much. First time I tried Creatine AKG I felt a boost too but I think I was probably just slightly deficient in creatine, there's no sense of energy boost at all when I eat grammes of that stuff.

Jack Black yeah I got that effect with NMN so perhaps the addition of akg isn’t as noticeable for me.  Mostly for me the amount of rest between sets is minimal now.  Similar to how I felt as a teenager.  

Michael When I boosted my creatine [akg] dose to what they said on the bottle, 2g before and 2g after I noticed some exercise benefit. It's nice rushing up the hill past noticeably younger people who are panting away. :D  

Jared How was the pricing from China which is I think the source for almost all of it. Alive by Science says on the package (100mg at a time) Made in USA. Did you have to buy a Kilo? I have 2 good sources but I have to buy a kilo at a time, so for NMN that is a $1,000 at a time and that's what it cost retail here now. Alive by Science, DoNotAge and Prohealth, the best sources.

John Ramos if I remember correctly my last order was about $700 US for a kilo.  You can buy smaller amounts but the price per gram increases.  

Jared That's actually cheap...It's basically $1,000 here. Alive by Science says on the package Made in the USA. Did you find them on Alibaba or Made in China or another?

John Ramos I found them on alibaba.  I basically ordered a bunch of samples from different companies and determined which samples were legit.  NMN has a very distinctive taste with no flush.  Then I ordered a kilo from the company that I felt most comfortable with.  The NMN effect hasn’t dropped off since I’ve been supplementing it.  

Jared What effect did it have on you? You mind sharing which company you used? It does have a distinctive taste, sort of a citrus taste and very fine, fluffy. The last I got from ABS had a stronger citrus taste and dropped to the bottom a cup in a lump, had to agitate it to mix. Also, ABS said water degrades it which I found to be strange. They got huffy when I pointed that out.

John Ramos for me the effect has been nothing short of miraculous.  Whatever issues I had prior, they were definitely NAD related.  The 1st thing I noticed was my gait improved.  My walking was faster and I was lifting my feet higher.  My chronic back pain disappeared, chronic fatigue vanished, clearer thinking, better focus, no after lunch lethargy, better mood and disposition, less fixation on stressful things, increased strength in both amount of weight and number of reps, better cold tolerance.  I basically don’t shiver anymore, and many more things I can’t think of off hand. 
 

I forget the name of the company off hand. It’s a Chinese name. But here is my contacts email. Her name is Olive, email is sales02@sxherb.com

Jared WOW, all I can say is you had fantastics results, 1g per day or more? And thanks for the info...Another thing to look at is Fermented Wheat Germ Extract - Spermidine, inexpensive way to get it. Have a kilo of it, 1g/day.  If you look at Amazon, they want an arm, leg and those 2 other parts for it, crazy, they're making bank on it. Do you mind if I ask how old you are, I can tell you're really into in as I am. I'm 75, so time is of the essence. 

John Ramos yes 1g per day.  I’m 44 and I felt like I was 60.  It was a strange situation because I look much younger but I felt much older.  It occurred to me one day that nobody else my age was feeling as bad as I did.  Just blind luck trying NMN, but I guessed right.  Yes I’ve been taking spermidine for a few months now and I haven’t really noticed anything.   Same with akg, urolithin a abd a bunch of others.  NMN was the 1st product I tried.  NR gave me a bit more energy boost on top of the NMN.  Otherwise nothing else has made a perceivable difference.  

John Ramos one other thing that improved with NMN was my muscle knots.  I was riddled with knots in pretty much every muscle especially my back.  They are mostly gone and pretty much 100% pain free.  I feel like it restored my muscle health and function.  

Jared You mean cramps or knots a masseuse or chiropractor takes out? I think most of knots are caused by stress?  Are you taking enough magnesium? Have you had a fairly physical work life? We got to get you feeling like your 40! LOL

John Ramos yes your typical knots. I think they are a mitochondrial issue.  A muscle dysfunction issue.  Nothing touched those knots except NMN. 

Jared any nocturnal leg cramps? If so, was that improved by NMN?

chuck stanley not for me unless I played sports that day. For me it was more chronic knotting and pain in my back, neck and limbs vs cramps.   

Jared How much Magnesium and type are you taking, it REALLY important for muscles.

John Ramos I took ZMA for a decade.  I don’t remember the dosage of Mg in that.  It made a little bit of a difference.  But nothing drastic. Now I don’t take any actually.  

John Ramos now that you’ve got me thinking about it NMN has changed how I perceive stress.  So the same stresses with the same start and finish but it’s how I perceive it that has changed.  I tend not to dwell anymore.  I liken it to my kids who you can yell at for something and then 5 min later they’ve forgotten.  The stress happens and then I forget.  I don’t think about the office after I leave until the next day when I arrive.  No more Sunday blues etc.  that’s another change especially considering the last couple years where my colleagues have all been more stressed and I’ve been less.  At least I perceive it that way now.  

Jared Good for you, stress is one of the worst things for our overall health both physical and mental. Now...I'm going harp on you about magnesium, it's needed for almost all functions in the body. I found a good one and I suggest you take it, cheap too.  Source Naturals Magnesium Malate - 3750mg Per Serving - Essential Magnesium Malic Acid Supplement - 180 Tablets, you can get it in capsules but you need six of them. I really think it will make a difference in your situation. Take 3 fo get full %DV.

John Ramos alright alright I’ll grab some and put it back into my regime.  Can’t hurt.  

Another thing that I just remembered was that prior to NMN I used to do a 20 min stretching session every single morning.  It helped with pain relief and to loosen things up.  Now I never stretch. It just doesn’t occur to me.  I used to use my therapro all the time too.  Now I almost never use it.  

Also I don’t seem to suffer from the low light levels in the winter anymore.  Up here In Canada the light levels get pretty low in winter and every year I’d be starved for sunlight by January.  It seemed to get worse every year.  I’d take a sunny vacation every winter just to recover.    My guess is that the NMN reset the circadian photo sensor in my eyes.  I think as you age it becomes less sensitive and you require brighter light to trigger it. I’d have trouble sleeping in the winter because of it.  It was something that didn’t bother me as a child but highly affected me as an adult.   My eyes seem to be able to determine the time of day by the winter light levels again.  

Jared Sounds like NMN is a saviour for you, good. I also just a found a cheaper version of the same mag, Nature's Life Magnesium Malate -- 1300 mg - 250 Tablets
SKU# 040647006874 2pcs for $39.98, it only 2 tablets/day for the same dose - On Vitacost.com

Jared I got nailed by the posting review algorithm for the second magnesium post.  Couldn't do anything for a few days. The fixed it when I contacted them. 

John Ramos no worries 

Jared Here, check this out, Longevity Supplements

Magnesium Pills 2,300/mg of Magnesium Malate gives you 400mg of elemental Magnesium 98% DV
 

ALA – caps 600mg/day

Fucoidan caps 1g/day Sirt 6 activator

Glycine powder 1/g/day now, upping to 2g when it arrives.

Berberine Caps 1,200mg/day, trying to get metformin instead. Maybe someone else can help with this one.

Ca-AKG powder 2G/DAY

Fermented Wheat Germ Extract 1g/day, I bought a Kilo, check the prices on Amazon, Hahaha

TMG powder 1.5g/day

Trans-Resveratrol powder 1g/day

NAC 2G/day, I have this in 1g tablets

NMN powder 1 – 1.5g/day I think 1.5 is more appropriate, you need to take a NAD+ test ($200) to determine, if you taking enough NMN, Richard (Modern Healthspan) took the test and upped his to 1.5g/day, I suspect I would also test the same.

Fisetin, Caps 20mg/kilo of body weight, 2 days in a row, with a 3-month break, you don’t want to completely clear out senescent cells, having some is beneficial and anti-cancer 

Apigenin, this is one I’m really conflicted about, 16g of dried parsley is a daily dose, but that’s too hard to take. I can’t figure out a low-cost method of taking this in adequate amounts, maybe some else has a solution?

Most of the loose powders I take with Trader Joes full fat Honey yogurt  

All of these have been heavily researched, I’m taking these amounts because of that fact. I hope I’ve covered everything.

John Ramos nice list you’ve got there.   Metformin, apigenin and fisetin you can get from the source I posted in one of my previous replies if you want.  
 

In regards to akg I was listening to an interview with the one of the researchers looking at this compound and he was saying a better method of Delivery may be by dissolving it in your water and drinking it over the day.   That a continuous source of it through the day may be more beneficial than taking it all at once.  

Jared You mean India mart? I think I have 1 kilo of Metformin from a Chinese drug company for $15 fob... waiting for payment link.

It may be more beneficial taking AKG over time but I'm just trying to keeps it simple, it supposed to add a spectacular amount of lifespan 20%?

John Ramos Hi, where do you get the 20% figure for AKG life extension? The info I've seen was 5% for male mice. Also, where do you source your Ca-AKG from? I've been buying the Kirkland stuff but it's relatively expensive. 

Jack Black First of all, how old are you just for a reference...

Here is one great video, from "The Sheekey Science Show", you should subscribe, she is a researcher and sometimes a little too complicated...but easier to understand on this one. I've watched and read a bunch and a few of them actually said about 20%, a lot of bang for the buck on this one.

https://youtu.be/3I7TxBT8FmI

And I purchased CA-AKG from my Chinese supplier I've been buying from since 2015.

I think it was about $80/Kilo, she also says it's the AKG, doesn't need to be CA-AKG but I've got CA-AKG so that's what I'm taking.

Hope this helps...

John

@John Ramos As reported in the forum,  I and others were cheated by a Chinese rapamycin powder supplier recommended by several people on this forum. Being a slow learner, I tried bargain hunting again with a different Chinese supplier...here is what happened: (from my recent post on the AKG thread):

"I was given a very good price on Ca-AKG powder from Xi'an Biohorlden Industry&Trade Co.,Ltd.  After a convincing correspondence with their rep and having received a thorough and impressive COA on their stationery showing high purity, I was ready to buy a kg for $120 plus shipping.  

Fortunately, I decided to take one final closer look at the COA. Although the CAS number was correct for Ca-AKG, the chemical formula and molecular weight were wrong. They were for Calcium Acetate Lactate! The Certificate had obviously been partially altered.

Worse than losing some money on a useless product is that I would have lost the years of benefit I would have obtained from AKG."

We are all tempted by the great prices on Chinese powders, but you take a great risk unless you are willing to have the product tested. 

John Ramos I'm 50. Thanks for the link above, I am a fan of Eleanor. 80 bucks a kilo sounds like a great price.

John Hemming yes inflammation is raising CD38 levels which is destroying NAD+. The science isn't clear why but it could even be a defense mechanism by the body; high NAD+ levels in inflamed tissue might help cancer form. Tackling the inflammation for example by reducing unhealthy body fat would be a good way forward. You can also limit CD38 with apigenin rich foods like parsley.

John Hemming 

Alive by Science, DoNotAge and Prohealth, the best sources.

Reply  Like

John Hemming Lot of research suggesting high dose melatonin helps fight cancer - which may be an inflammatory response. Recently upped my dosage to 120 mg a night. Really changed my deep sleep pattern. Will be interested in measuring inflammatory markers in January

Michael The amount I take each night (it is almost invariably after midnight and before 8am) varies from 0 through to over 400mg.   Melatonin is a circadian hormone and it is important not to undermine the circadian cycle by taking it at the wrong times.

Michael melatonin has a wide range of effects. Some are immediate and some happen over a longer period. The time it is taken is critically important as to the effect.  Two suppliers provide suppositories with 200mg or 400mg, but i dont know the bioavailability. My priority when i take melatonin is to ensure i get good enough sleep in order to be fully functional the next day. I normally achieve this.  It does affect different people in different ways. I will often take it more than once during the night.

Michael yes 60 before bed and another 60 when i wake in middle of night

Paul Beauchemin that is fascinating. So 60 mg (not er I assume) before bed, and another 60mg when you wake up, as many of us do for a bathroom call. And that doesnt adversely affect your circadian rhythm? Sorry, I guess you already answered that.

Since I have difficulty returning to sleep, or when I do it is not of sufficient duration, that sounds very promising. My fear was that a large middle night dose would give me a hangover, but that hasnt been a problem? Did you need to keep increasing your dosage in order to get back to sleep or because you wanted to maximize other benefits?

Michael no the timing is key to this. My priority is good sleep, but i also take more for the side effects. I dont think taking it before sleep is helpful.  Sometimes I sleep well and take no melatonin. I am currently experimenting with some subtleties.

Michael only effect is deep sleep went from 30 min per night to 3 hours

feel great during the day

chuck stanley not for me. Seems I get a cortisol spike about half hour before I wake. One reason I've never needed coffee. No change at all with large dose melatonin.

Was taking 120 before bed. One issue I have had these past few years is waking in middle of night and not being able to fall back asleep. Saw a suggestion on Longecity to take a dose when I woke in middle of night and so I split the dose and it has made a huge difference

Paul Beauchemin 

     Are there any published studies indicating that taking Melatonin at the dose level of 120 mg or more is a good idea?  I thought that it was a hormone that was most effective at the ~1 mg dose level.  FYI, I take 3 mg of Life Extension's 6-hour time-release Melatonin at bedtime and sleep well through the night.

JGC The reason I take large amounts of melatonin is that I like the side effects.

I did a video about Melatonin

https://www.youtube.com/watch?v=tfEJcUDVUoo&t=153s

It is the case, however, that there is published research that Melatonin can demethylate the epigenome. (for Radishes, but the chemicals are the same).

I got into this because I took quite a bit of Melatonin for sleep and noticed I was growing dark hairs in places where I have  not had hair for a long time.  Only a few, but very gradually I am getting less bald mainly with the growth of a very fine layer or white hairs, but also some dark hairs.

I was not ever particularly concerned about hair loss as my father went bald and I expected to do this.  However, I see this as a sign of an improvement in cellular health more generally and I would like my organs to function well.

An interesting relevant point is high frequency hearing.  This is a specialised hair cell question that is easy to measure.  Sadly I did not measure this when I started.  However, I am 61 and can hear 14 kHz which is more of a 40s thing.

Melatonin is, however, a circadian hormone.  I am of the view that I want to go to sleep on endogenous Melatonin so I only take Melatonin when I wake up in the night.  I don't think it is a good idea to take it before going to bed.

More recently I have managed to kick the alcohol rebound into touch, but I need really to have more nights where I don't drink as ethanol is not good for health even if hedonistically it has merit.

John Hemming 

    Interesting. 

    I note the NIH says that the biovailability of Melatonin is about 15%, and it's solubility in water is about 0.1 mg/ml.  Therefore, there is not a strong reason to bother taking it sublingually, which will only give a bio-boost of 2 to 4.  My daily dose of 3 mg therefore delivers about 0.5 mg to the bloodstream, which is about right for a hormone.

    The Mayo Clinic says that the most common Melatonin side effects are headache, dizziness, nausea, and drowsiness (that's the point).  Less common side effects include short-lasting feelings of depression, mild tremor, mild anxiety, abdominal cramps, irritability, reduced alertness, confusion or disorientation, and abnormally low blood pressure (hypotension).  They also mention drug interactions with anticoagulants and anti-platelet drugs, anticonvulsants, contraceptive drugs, diabetes medications, and medications that suppress the immune system.

    Be careful.  I would think that taking a large dose like 120 mg per day might produce the chemical equivalent of jet lag, screwing up your circadian clock.

JGC Without going into the question of how you come to your conclusion. I can say experimentally it is not true.  However, it will vary from person to person.

JGC there are many studies that looked at high melatonin levels and cancer. I have PC and that is what interested me. The side effect of deep sleep is a pleasant surprise.

JGC no, none of these side effects for me (except longer deep sleep). I monitor 30 biometrics daily so quite noticeable if something changes.

I experimented with 1-10 mg for years and never improved my sleep until now.

John Hemming 

I've been taking 120 mg Melatonin now for about 2 months.  Started 4 months ago with 3, then 6, then 10, then 20, and so on until I reached 120.  The purpose is to control lutenizing hormone.  Jeff Bowles theorizes that excess lutenizing hormone causes Alzheimer's, and Melatonin can be used to reduce that excess.  See his ebook "Extreme Dose!  Melatonin The Miracle Anti-Aging hormone...", available in Kindle format at Amazon.

A bit of background on how I got to this point. 14 years ago I started taking TA-65 to slow telemere shortening.  One of the effects is particularly vivid dreaming.  Then I found out that TA-65 is cycloastragenol, which is available at much lower price.  So I ordered some powdered cycloastragenol and put it into capsules.  But in order to get the same dreaming effect with my DIY capsules I had to take about 5 times as much as the TA-65, which essentially wiped out the price advantage.  Then I discovered enteric effect capsules.  Enteric effect capsules filled with cycloastragenol seemed to be equally potent to TA-65 as measured by my dream-o-meter.  So I've taken about 45 mg of cycloastragenol in enteric capsules for the past 12 years or so.  Last few months I've been taking TAM818 capsules instead of the cycloastragenol.  Note also that I've taken 50,000 IU vitamin D3 daily for the same 14 years.

With the cycloastragenol my sleep pattern has been about 7-9 hours per night, with 1 or 2 wakenings.  Each wakening occurs with a dream, and resuming sleep is easy.

Add the 120 mg of Melatonin before going to bed and the pattern is the same.  Maybe a little more dreaming.  I've skipped the Melatonin on several occasions and there was no change in my pattern.  Still go to sleep normally, wake several times, and go back to sleep immediately.  Wakening seems to occur on 1 1/2 hour boundaries, like maybe 4 1/2 hours, 6 hours, and wake up for the day at 7 1/2 or 9 hours.

Haven't seen any bad side effects, and the potential of reducing Alzheimer's is good enough for me to continue.  I'm 77, male.  Women would take maybe 75 mg.
 

Paul Beauchemin There is a difficulty in that the side effects are difficult to spot as they occur gradually.  There is quite a bit of research, however, that justifies them.  The only one I can certainly say is melatonin is a reduction in gingivitis that occurs from taking it sublingually as this is an effect that can be seen by whether or not I take any melatonin that way. (and to some extent how much).   When I started growing hair where I had been bald for about 20 years I could not guarantee that this was melatonin, but there is research that points at this.  There are also issues about needing a combination of inputs to get an output.  If you are not getting the right K2 vitamins then maintaining bone structure will not be as easy.

RobH Without checking the research from memory I think there are a number of cognitive benefits from good sleep.  Which of those are really melatonin and which not affected is hard to determine.

Michael Thanks for that I only do videos where I think I have something to add to the debate rather than just a repetition of what someone else has said.

John Hemming excellent video. Several more reasons for me to take high doses in the papers cited.

Reducing the cortisol wakening effect is one thing I've been searching for without success. I have a very sharp response half-hour before waking which spikes my glucose. Melatonin has no effect on this.

Paul Beauchemin I also did a video about sleep hacks in which I talk about using Cox-1 inhibitors say about 1-2 hours before the CAR to minimise it or after it has happened to try to get back to sleep.  Asprin is the one with the most research, but Resveratrol is also a cox-1 inhibitor.

I also have an interesting experiment going on which I want to patent to get a lot more control on the CAR and the interplay between sleep and waking.  I would like to patent this so that if the pharma companies take up the idea some money goes back into n==1 self hacking research more generally.   I cannot get the patent if I publish the idea (before applying for the patent) so i you would like to try it it would be off forum on a confidential basis.   Once the final patent is applied for then I will publish the details anyway. 

John Hemming thanks, unfortunately, aspirin causes bleeding for me. Look forward to your experiment

Paul Beauchemin you could try resveratrol, but that might also cause bleeding.

John Hemming 

    My conclusion (which is really a conjecture) was based on my attempt to understand the mechanism behind the sleep-inducing properties on Melatonin.   As I recall, when Melatonin first became available in the 1990s, it was characterized as a natural hormone that had been studied in the context of sleep regulation at oral dose levels of around 200-500 micrograms.

    Hormones attach to receptors on the system of cells that they are affecting.  If those receptors become over-saturated, that negatively affects the normal behavior of the system that the hormone is targeting.  It seems to me that that should happen when one takes 120 mg of Melatonin per day.  But, admittedly, that's just a conjecture.

JGC You are right in that receptors can get washed out.  However, Melatonin also acts in ways other than a hormone.  For sleep it emphasises the effect of GABA.

John Hemming that’s really interesting about the regrowth of pigmented hair.  We’ve seen other reports of similar from what was concluded to be a reduction of stress.  But I wonder whether the reestablishment of circadian order might be the key.   I suspect circadian disorder is a huge component of healthspan. It’s all just speculation on my part.  
 

Jared It was not that many hairs, but it is a gradual process that does not appear to have halted yet.  My own hypothesis is that this arises probably at least in part from a demethylation process.

John Hemming yeah I would guess that whatever epigenetic change resulted in hair loss has been at least partially reversed. 

Jared Hair is I think a particularly complex aspect of the body that is an indicator of health.   That is why I think high frequency hearing loss tests are a good test for general health (and very easy to do).  Sadly I have only tested this more recently some time after I started my protocol.

Michael yes 

John Hemming I’m a practicing tooth doctor and I’d agree that  melatonin, among almost anything you ingest, will impact the oral microbiome and contribute to general health. I suspect the benefits may at least partially be from some sort of bacterial metabolites that reduce inflammation in the gingiva.  Just like the gut, the oral microbiome also has a circadian cycle where the proportions of certain types of bacteria change throughout the day/night.  

Michael the major issue with implants is bone health. Both systemic and microbial factors play a role.  Surprisingly Age doesn’t seem to be talked about as much of a risk factor as does bone quality and healing ability.   That being said Diabetes and perio disease (diseases of aging) greatly increase the risk of implant failure.  We consider these plus smoking to be the greatest risk factors.  
I haven’t seen any data on melatonin or rapamycin in relation to implants (that doesn’t mean it’s not out there) but I would surmise that anything that restores youth to bone would be beneficial.  There is some literature on a significant benefit of resveratrol in perio disease which I think would also pertain to implants.  

Jared A lot of body systems benefit from the availability of a number of molecules.  For example bones need vitamins D3 and K2 (mk4 and mk7) for handling calcium as well as melatonin to get the balance between osteoclasts and osteoblasts right.  I have seen suggestions that K2 mk4 is particularly helpful for teeth.   

John Hemming yes that’s true.  In fact it’s the fat soluble vitamins A, D, K and E that matter most for facial growth.  They are mostly found in properly raised animal fats.  It’s I think why there has never been a truly vegan society until now.   The ancients knew the importance of these things.  Fats were once covered above all. 
A dentist by the name of Weston Price wrote about the importance of the fat soluble vitamins way back in the early 1900s.  He travelled the world analyzing the effects of modern vs ancient diets on facial growth.  He had the privilege of seeing 1st hand the changes in indigenous peoples as they converted from traditional to modern diets.  It’s an interesting read of anyone is interested.  

Michael yes so smoking more so than anything else really changes the physiology of the mouth.  The biggest change I notice clinically is the decreased vascularity of the tissues.  The gums and bone don’t bleed well and I suspect this is the reason why implants fail.  Any type of trauma results in delayed and sometimes inadequate healing.  It’s also why perio disease is more prevalent in smokers.  

Michael yes they we can get them to integrate.   But we always tell the patient there’s a greater chance of failure and it may have to be removed and replaced.   

John Hemming Reading your comments here about K2, which is extracted from natto, also the source of nattokinase (nattokinase decreases plasma levels of fibrinogen), reminded me of an article I saw recently regarding fibrinogen and gum and bone disease. 

https://www.sciencedaily.com/releases/2021/12/211223143106.htm

Disarming a blood-clotting protein prevents gum disease in mice

"Blocking function of a blood-clotting protein prevented bone loss from periodontal (gum) disease in mice, according to research led by scientists at the National Institute of Dental and Craniofacial Research (NIDCR), part of the National Institutes of Health. Drawing on animal and human data, the researchers found that buildup of the protein, called fibrin, triggers an overactive immune response that damages the gums and underlying bone. The study, which was published in Science, suggests that suppressing abnormal fibrin activity could hold promise for preventing or treating periodontal disease, as well as other inflammatory disorders marked by fibrin buildup, including arthritis and multiple sclerosis."

Dan Nave Only Mk7 comes from Natto.  It is possible to supplement with MK4 and mk9 as well.  Certain foods  mainly hard cheese also have the longer chains of isoprenes, but that varies quite  bit.  I think the longest chain that is seen is MK-13.  However, I don't think there is good research on anything other than MK-4 and MK-7.

John Hemming Excuse me?  Natto....Nattokinase???... 

"Nattokinase (NK), the most active ingredient of natto, possesses a variety of favourable cardiovascular effects and the consumption of Natto has been linked to a reduction in CVD mortality. Recent research has demonstrated that NK has potent fibrinolytic activity, antihypertensive, anti-atherosclerotic, and lipid-lowering, antiplatelet, and neuroprotective effects. "

But, nevermind...

Dan Nave I don't think Natto produces MK4, however. Obviously Natto has other things in it, but as far as the menaquinones go I think only mk7 comes from natto.  Things like hard cheese can produce mk4, 7 8 and 9 at times.  That depends upon the fermentation.

Michael there’s also a little bit of data on rapamycin and perio disease although I think the field needs more human data before it becomes something that would be generally recommended.  

JGC There is a good point in that quality control of supplements is variable.  It comes down to identifying brands which offer third party testing certificates, but that does not mean that Melatonin itself is harmful.   The body creates Melatonin from Seratonin. 

John Hemming 

    In that context, you might list the suppliers of Melatonin you know of that DO provide 3rd party lab tests of their product.

JGC It is possible, but I have not looked at this.  I use Eurovital which to me is reasonably consistent.

JGC I am not sure 5HT can cross the BBB, it could be 5HTP you are referring to, but even then you need to inhibit the AAAD enzyme to have neurological effects at a reasonable dose. Perhaps melatonin is made in the factory from 5HT. Anyways, it seems more might be better as it clears toxins from the brain during sleep… a lack of which could be the cause for dementia.