955 replies to this topic

[judge]

I lost my data when my last computer fried from an electrical surge.  But I found it all using google.  Basically, it was Man's first antibiotic and it was used as a blue die. It recharges your mitochondia,  I call it a nap in a glass.  When I do not get enough sleep and really need a nap after lunch but do not have time, I drink one or 2 glasses of diluted methylene blue and it just makes you feel normal.  It does not make you edgy like coffee and you go back to feeling sleepy again about 4 or 5  hours later.  The dosage I use is 30 drops diluted in a gallon of water.  Plus it is really cheap, I use the Kordon brand and one bottle will probably last me 20 years lol    This stuff is really candy to your mitochondria!  You can get some good insight on other benefits by reading amazon reviews, bit unscientific but it is easy to research anything you find interesting.  Good Luck!

 

Methylene Blue | Kordon

 

 

Specifications & Stability

SPECIFICATIONS
Contains zinc free, chloride salt of Methylene Blue. Provided as a 2.303% water solution.

 

Edited by judge, 14 December 2021 - 04:50 PM.

[Dallasboy]

 

I lost my data when my last computer fried from an electrical surge.  But I found it all using google.  Basically, it was Man's first antibiotic and it was used as a blue die. It recharges your mitochondia,  I call it a nap in a glass.  When I do not get enough sleep and really need a nap after lunch but do not have time, I drink one or 2 glasses of diluted methylene blue and it just makes you feel normal.  It does not make you edgy like coffee and you go back to feeling sleepy again about 4 or 5  hours later.  The dosage I use is 30 drops diluted in a gallon of water.  Plus it is really cheap, I use the Kordon brand and one bottle will probably last me 20 years lol    This stuff is really candy to your mitochondria!  You can get some good insight on other benefits by reading amazon reviews, bit unscientific but it is easy to research anything you find interesting.  Good Luck!

 

What is the recommended dose for MB?  I see a wide range.  What would one glass of your MB drink be in dosage?

[judge]

What is the recommended dose for MB?  I see a wide range.  What would one glass of your MB drink be in dosage?

quite small, i forget the calculation, if you google nootropics and methylene blue you may find the forum i found this info.  you can try to calculate it yourself, use the percentage of the solution in the bottle and divide the gallon of water with the 30 drops from a dropper. This like rapamycin is off label usage and there really is no recommended dosage.  Sorry but if you want answers you are going to have to spend a few hours online researching.

[Dallasboy]

quite small, i forget the calculation, if you google nootropics and methylene blue you may find the forum i found this info.  you can try to calculate it yourself, use the percentage of the solution in the bottle and divide the gallon of water with the 30 drops from a dropper. This like rapamycin is off label usage and there really is no recommended dosage.  Sorry but if you want answers you are going to have to spend a few hours online researching.

 

Ha.  Well that's the thing, I have spent hours reading about MB dosing, and it seems to be a wild range of 200mcg to 15mg.  I thought I would ask someone who just recommended to another person to take it....right?!?  I mean, you tell someone to take it....then when asked your recommended dose, you tell someone else to go research yourself like you don't have any knowledge about it.  If you are going to recommend something to someone, tell the full story.  /end

[FrankT.Hippo]

Ha.  Well that's the thing, I have spent hours reading about MB dosing, and it seems to be a wild range of 200mcg to 15mg.  I thought I would ask someone who just recommended to another person to take it....right?!?  I mean, you tell someone to take it....then when asked your recommended dose, you tell someone else to go research yourself like you don't have any knowledge about it.  If you are going to recommend something to someone, tell the full story.  /end

 

Ya.

 

I see in high does it acts as an oxidant. So I have to avoid that.

 

I will have to do some research then.

 

I see that science bio has it: https://science.bio/...lution/ref/613/

 

I usually go there -- I don't screw around with low end or dubious brands, given underlying problems. 

 

Thanks. I will look into it though.

Edited by FrankT.Hippo, 14 December 2021 - 09:31 PM.

[judge]

Ha.  Well that's the thing, I have spent hours reading about MB dosing, and it seems to be a wild range of 200mcg to 15mg.  I thought I would ask someone who just recommended to another person to take it....right?!?  I mean, you tell someone to take it....then when asked your recommended dose, you tell someone else to go research yourself like you don't have any knowledge about it.  If you are going to recommend something to someone, tell the full story.  /end

Sorry didn't have much time was heading out to an appt and didn't think the answer through.  I believe my measurements give about 30mcg.  So the exact amount I take is as follows,  30 drops from a standard medical dropper, so that is pretty darn close to 1.5 ml.  I use a full gallon jug full of reverse osmosis water add the drops and shake it up.  Then i pour a 12 ounce glass and drink it. If I know I have to do a hard workout and I am already tired i drink 2 glasses.  I hope this helps, I am not a doctor and am just sharing something I personally have had great success.   It is very subtle, it does not have any taste and you don't feel anything, I just feel normal and am not tired.   Good Luck!

 

Low-dose methylene blue stimulates mitochondrial respiration by donating electrons to the electron transport chain.

:text=Methylene%20blue%20readily%20crosses%20the%20blood-brain%20barrier%2C%20builds,Ehrlich%20and%20Ramon%20y%20Cajal%20in%20the%201890s.' class='bbc_url' title='External link' rel='nofollow external'>Frontiers | Protection against neurodegeneration with low-dose methylene blue and near-infrared light | Cellular Neuroscience (frontiersin.org)

 

 

Methylene blue, a potential therapeutic target for mitochondria dysfunction - PubMed (nih.gov)

 

 The beneficial effects of electron carrier compound methylene blue (MB) are proven in many disease models where mitochondrial involvement has been detected.

Bioenergetic Impairment of Triethylene Glycol Dimethacrylate- (TEGDMA-) Treated Dental Pulp Stem Cells (DPSCs) and Isolated Brain Mitochondria are Amended by Redox Compound Methylene Blue † - PubMed (nih.gov)

[Dallasboy]

Sorry didn't have much time was heading out to an appt and didn't think the answer through.  I believe my measurements give about 30mcg.  So the exact amount I take is as follows,  30 drops from a standard medical dropper, so that is pretty darn close to 1.5 ml.  I use a full gallon jug full of reverse osmosis water add the drops and shake it up.  Then i pour a 12 ounce glass and drink it. If I know I have to do a hard workout and I am already tired i drink 2 glasses.  I hope this helps, I am not a doctor and am just sharing something I personally have had great success.   It is very subtle, it does not have any taste and you don't feel anything, I just feel normal and am not tired.   Good Luck!

 

Low-dose methylene blue stimulates mitochondrial respiration by donating electrons to the electron transport chain.

Frontiers | Protection against neurodegeneration with low-dose methylene blue and near-infrared light | Cellular Neuroscience (frontiersin.org)

 

 

Methylene blue, a potential therapeutic target for mitochondria dysfunction - PubMed (nih.gov)

 

 The beneficial effects of electron carrier compound methylene blue (MB) are proven in many disease models where mitochondrial involvement has been detected.

Bioenergetic Impairment of Triethylene Glycol Dimethacrylate- (TEGDMA-) Treated Dental Pulp Stem Cells (DPSCs) and Isolated Brain Mitochondria are Amended by Redox Compound Methylene Blue † - PubMed (nih.gov)

 

Thank you!

[DJSwarm]

Thanks, waverock. It's always good to be aware of potential side effects. Here's a video that was released about a year ago that collects tons of studies about MTOR inhibitors and makes sense of them. As he says several times, lower doses and intermittent use has the opposite effect (in particular on immunity) as high, prolonged dosing. The video is long - almost an hour - and it's all very good. But if you want to skip ahead to his main conclusions, it really gets interesting 47 minutes in: 

Interestingly (to me at least) he starts out talking about Lyme Disease. What does that have to do with aging? It's all linked together, as I can demonstrate by sharing a brief version of my own story. About ten years ago, just before I turned 50, I discovered a tick between my toes, and it had been there for several hours. A month or so later, I noticed a circular rash on that leg. Convinced that I had Lyme, I got tested, which came back negative. Only years later, I learned that the test that most US doctors perform is useless. Two years later, i began having very early symptoms of Parkinson's.

Recently I saw a study which showed that the brain's normal response to serious infections (Lyme bacteria can invade the brain) can cause the mis-folded proteins that triggers Parkinson's (and AD). After that, it's a cascade effect. 8 years into it, i'm learning about Rapamycin, and I'm hoping that it can trigger the autophagy cleanup that's needed. Anti-aging is just a happy possibility for me, not my immediate goal.

Rifampicin and Resveratrol Nasal Spray Prevents Dementia in Preclinical Study

[DJSwarm]

Rapamycin treatment, however, resulted in a significantly increased prevalence of vacuolization of tubulus epithelial cells [13], indicative of nephrotoxic side effects of rapamycin treatment.

It would be nice if you included your studies...

 

Rapamycin slows aging in mice Calls out a number of detrimental effects such as cataracts and testicular disfunction.

Sirolimus-Associated Testicular Toxicity Detrimental But Reversible Looks at testicular function specifically

 

The main thing I'm getting from this and similar studies is that you should not start while young or try to conceive while on rapamycin; and, you should not dose continuously and have plenty of breaks unless you are treating a disease and are willing to face possible detrimental side effects.

 

For example in Synergistic effect of rapamycin and metformin against germ cell apoptosis and oxidative stress after testicular torsion/detorsion-induced ischemia/reperfusion in rats an single dose was actually protective against testicular insult.

 

Metformin does seem to be synergetic (I'd love to see a test of rapamycin and berberine) and help with glucose rise from side effect level dosing. Resveratrol also seems to inhibit potential liver issues.  Rapampicin and Resveratrol Nasal Spray Prevents Dementia in Preclinical Study This is also synergetic in the trial and they give the surface area conversion for human dosing.

[DJSwarm]

Kind of a disappointed with Dr.Green

 

 

Already booked a flight after he agreed to see me at his new office in NY, upon later learning that I was only 40 he cancelled my appointment saying that I was "too young for rapamycine treatment."  What's the point of anti aging if you don't start treating it until you're very old?

 

Guess Im stuck with finding an Indian Pharmacy or hoping one of these Chineese group buys goes through, with not doctor to monitor my use.  

 

Undulating changes in human plasma proteome profiles across the lifespan

 

Short answer your blood proteins shift to the next stage of aging at 30, 60 and 80 according to this study.

 

Of course I can't find it now but I was reading that reversal of age related disc damage was better if initiate in middle aged mice over aged mice but both benefited, i.e. I'm not sure his position is valid.

[judge]

highly recommend Artemesia aka wormwood for lime

 

MANY ARTICLES ON IT, HERE IS A GOOD ONE

 

Artemisinin For Lyme Disease Treatment Protocol (nootriment.com)

 

If I had lime i would also take proteolytic enzymes, serrapeptase away from food and nattokinase with food, really cleans up the blood. makes it thinner too, so if you are on a blood thinner or aspirin stop those while on enzymes, fyi blood thinners and aspirin will kill you eventually, enzymes will help you live forever 

[DJSwarm]

I don't think mentioning other meds we take along with R is off-topic. I'm interested in BL too, maybe combining it with NR and R.

 

BL = Pau D’Arco, yes?

[DJSwarm]

I'm 40. Why wouldn't taking rapamycin help me?

 

It might help you but you might not notice since you aren't old enough to have age related decline.

Same with the other techs like D+Q or F. You accumulate senescent cells through out your life but tipping points seem to be at 30, 60 and 80.

However, in mouse studies even a single run seem to act as a kind of reset which lasted well beyond the initial dose.

Just me, but at your age I might do a short run once a year, ditto for the other technologies like D+Q, F for senescent cells and astrogalus / epitalon  for telomers.

[DJSwarm]

Arg - typo the nasal study is rifampicin not rapamycin - do not mix the two. sorry for the confusion

It would be nice if you included your studies...

 

Rapamycin slows aging in mice Calls out a number of detrimental effects such as cataracts and testicular disfunction.

Sirolimus-Associated Testicular Toxicity Detrimental But Reversible Looks at testicular function specifically

 

The main thing I'm getting from this and similar studies is that you should not start while young or try to conceive while on rapamycin; and, you should not dose continuously and have plenty of breaks unless you are treating a disease and are willing to face possible detrimental side effects.

 

For example in Synergistic effect of rapamycin and metformin against germ cell apoptosis and oxidative stress after testicular torsion/detorsion-induced ischemia/reperfusion in rats an single dose was actually protective against testicular insult.

 

Metformin does seem to be synergetic (I'd love to see a test of rapamycin and berberine) and help with glucose rise from side effect level dosing. Resveratrol also seems to inhibit potential liver issues.  Rifampicin (not rapamycin) and Resveratrol Nasal Spray Prevents Dementia in Preclinical Study This is also synergetic in the trial and they give the surface area conversion for human dosing.

 

[smithx]

Both of the first two studies used continuous dosing of rapamycin, which we already know can cause problems by inhibiting mTORc2. Intermittent dosing, as performed in this study:

 

Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice

https://academic.oup...1/7/876/2605199

 

and by most people who are trying this on themselves, seems to largely avoid this problem, and perhaps also the toxicity found in those studies.

 

The last study doesn't say that the detrimental results of the first two necessarily would be ameliorated by metformin. It's studying damaged caused by physical stress.

 

It would be nice if you included your studies...

 

Rapamycin slows aging in mice Calls out a number of detrimental effects such as cataracts and testicular disfunction.

Sirolimus-Associated Testicular Toxicity Detrimental But Reversible Looks at testicular function specifically

 

The main thing I'm getting from this and similar studies is that you should not start while young or try to conceive while on rapamycin; and, you should not dose continuously and have plenty of breaks unless you are treating a disease and are willing to face possible detrimental side effects.

 

For example in Synergistic effect of rapamycin and metformin against germ cell apoptosis and oxidative stress after testicular torsion/detorsion-induced ischemia/reperfusion in rats an single dose was actually protective against testicular insult.

 

Metformin does seem to be synergetic (I'd love to see a test of rapamycin and berberine) and help with glucose rise from side effect level dosing. Resveratrol also seems to inhibit potential liver issues.  Rapampicin and Resveratrol Nasal Spray Prevents Dementia in Preclinical Study This is also synergetic in the trial and they give the surface area conversion for human dosing.

 

[DJSwarm]

I'm now taking Nicotinamide Riboside (500mg)+ Pterostilbene (150mg) daily.  Pterostilbene is a more bio available form of reservatrol.  Dr. Sinclair has previously stated that he has been taking reservatrol for years.  Dr. Trammel stated in his paper that NR is the best precursor to increased NAD+ production.

 

...

 

You might want to check this:

...taking 500 mg NR twice daily for 6 weeks or combination of up to 500 mg NR and 100 mg pterostilbene per day for 8 weeks42,43. Whereas Dellinger et al.42 found that the combination of NR and pterostilbene significantly elevated low density protein cholesterol (LDL-C) in a dose and time-depended fashion42, no significant increases in LDL-C were seen following the administration of NR alone43.

 

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults (from Nature)

[PAMPAGUY]

Dr. Peter Attia has started taking Rapamycin.

So why not just take rapamycin every day?

• Peter says the following 3 things need to be true, if you’re taking the correct dose of rapamycin:
  • Glycemic response will be unchaged or improved (it shouldn’t get worse, which could happen if you take too much rapamycin)
  • Immunity should get better, not worse
  • Autophagy should increase (but there’s currently no way to measure this)
• One of the most obvious negative side effects of rapamycin is mouth sores (apthous ulcers) – Peter equates them to “super annoying canker sores”

What would be the correct rapamycin dosing?

• In the Mannick study, the negative side effects when taking 5 mg of rapamycin once per week, compared to taking 1 mg every day, didn’t seem to be that much worse
  • But taking 20 mg once per week vs. 5 mg once per week, showed no additional immune benefit (however there were more negative side effects)
• Matt Kaeberlein has done some studies on dogs, suggesting the optimal dosing in humans would be around 4-8 mg, in some sort of pulsatile/episodic fashion (every other day or every third day)
  • Why? – You don’t want to inhibit MTORC2 
    • If you dose with rapamycin every day, you don’t allow for TOR to be recirculated, and within a few days of consecutive dosing, you start to inhibit the creation of mTORC2
• So in short, there’s no side effects to taking too little (just a lack of benefit), but you want to be careful about taking too much
• If Peter were to guess the perfect dose: 4-6 mg every 4-7 days

Rapamycin Appears to Inhibit Senescent Cells

• Senescent cells are cells which are “basically bad actors”
  • They essentially mimic other types of cells, with a less effective version
  • So inhibiting them, would be a benefit

Can anyone take rapamycin?

• Yes – all you need is a presrciption from your doctor
  • We just need more data to indicate that we’re not taking too much/we’re taking enough

Does Peter take rapamycin?

• Yes (for the last 3 months), but he’s never written a prescription for it
  • “I’m relatively confident that the dosing I’m using is relatively congruent with all the data I’ve assimilated over the past 4 years, and speaking with some of the smartest people in the world”
  • He’s taking 5 mg (he doesn’t say how often)
• Why does he take it?
  • “For me and my risk appetite, I think the risk of not taking it is higher than the risk of taking it”
  • A good way to think about this – “Strong convictions loosely held”
    • Peter says, given new information/data, he’d be apt to change his mind very easily
• Has he noticed anything?
  • For the first two months, he had very bad mouth sores…and then they stopped
  • Nothing else
• Here’s what Peter has learned from a physician, also in NY, who regularly prescribes rapamycin – “the worse your glucose levels are starting out, the more of an improvement you can get”
  • What else is this doctor seeing? 
    • Patients are losing weight, their triglycerides are falling, insulin/glucose levels are improving as well as HA1c

Are there any cognitive benefits of taking rapamycin?

• “It’s a bit too soon to say”
  • Peter says it’d be a very interesting research question – What happens when you give rapamycin to people in the very early stages of cognitive decline?
  • “There’s definitely preliminary data that suggests, in certain models, that rapamycin is delaying the onset of cognitive impairment”

 

https://podcastnotes.../01/17/attia-5/

 

[PAMPAGUY]

VP, thanks for the info, but you have got some things wrong.  In Mannick study the elderly people were taking .5 mg (1/2) daily not 1 mg.  BIG difference. Also, elderly were taking 20 mg weekly and I agree that is too much for once weekly dosing.  Remember:  RAD001 used in Mannick is everolimus and is much weaker rapalog than rapamycin.   In the Dog Project, Matt Kaber has changed and is now dosing his dogs once a week at .15 mg x kg.  Here is a blog from Dr. Attia discussing Rapa with Dr. Kaeberlein.  Dosing is at 1:50. https://peterattiamd..._lHKPZf4oGlvr9Q

 

Dr. Blagosklonny and Dr. Green have both changed there dosing schedule to 20 mg. every 12-14 days.  The reason for this is to get the "spike" of rapa in the blood to get past the blood/brain barrier in the brain to inhibit Tor 1 in the hippocampus portion of brain which is thought to control ageing.  Dosing and schedules will change as we learn more.  Dr. Blagosklonny on his Twitter feed stated, "the most important rapa developments in 2022 will be higher intermediate doses of rapa along with rapalogs that will inhibit Tor 1, but not Tor 2.  

Edited by PAMPAGUY, 12 January 2022 - 07:44 AM.

[DJSwarm]

I do, theres much more that I take but, I only wanted to touch on what I felt was very related to anti-aging. Horsetail, pomegranate, folic acid, vitamins A and C. Stopped taking K2 when I read about the clotting from the coronavirus.

For the virus I have Ivermectin, another antiparasite med, and of course Zinc Picolinate.

If I feel any muscle cramping I take calcium or magnesium malate.

The list goes on and on. I have things for mucus buildup, kidneys, liver, and more.

 

mis-dosing Ivermectin can kill you and Ivermectin dose NOTHING for covid 

 

Things which do work - #1 full vaccination with booster, CBD (inhibits ACE2 binding, viral mRNA replication and IL-6 (the source of the cytokine storm)), Viagra, melatonin (inhibits ACE2 binding), mechanical removal via a standard nasal douche using 1% no tears, no fragrance baby shampoo and gargling with old skool Listerine (best result) or antiseptic mouthwash (used immediately after suspected infection and then repeat periodically to keep shedded nasal and mouth viral load down).

 

Tested only in vitro but surprisingly effective, lactoferrin (do NOT overuse or give to small children/infants) + Benadryl - killed 99% of the virus infecting epithelial cells - in vitro - not yet tested in vivo.

[DJSwarm]

Undulating changes in human plasma proteome profiles across the lifespan

 

Short answer your blood proteins shift to the next stage of aging at 30, 60 and 80 according to this study.

 

Of course I can't find it now but I was reading that reversal of age related disc damage was better if initiate in middle aged mice over aged mice but both benefited, i.e. I'm not sure his position is valid.

 

Here we go:

Rabbits Rapamycin prevents the intervertebral disc degeneration via inhibiting differentiation and senescence of annulus fibrosus cells

Mice Effects Of The Anti-aging Agent Rapamycin On Disc Matrix

 

And similar results from mice with D+Q Long-term treatment with senolytic drugs Dasatinib and Quercetin ameliorates age-dependent intervertebral disc degeneration in mice

 

No dr and not medical advice but if my mouse or rabbit had degenerative disc disease I go earlier on the intervention, rather than later.

[DJSwarm]

Both of the first two studies used continuous dosing of rapamycin, which we already know can cause problems by inhibiting mTORc2. Intermittent dosing, as performed in this study:

 

Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice

https://academic.oup...1/7/876/2605199

 

and by most people who are trying this on themselves, seems to largely avoid this problem, and perhaps also the toxicity found in those studies.

 

The last study doesn't say that the detrimental results of the first two necessarily would be ameliorated by metformin. It's studying damaged caused by physical stress.

 

Slow down cowboy and read my part before you get excited: "The main thing I'm getting from this and similar studies is that you should not start while young or try to conceive while on rapamycin; and, you should not dose continuously and have plenty of breaks unless you are treating a disease and are willing to face possible detrimental side effects."

 

"[W]hich we already know can cause problems by inhibiting mTORc2;" and yet I see PLENTY of people reporting mTORc2 side effects by trying to push to and hold the edge. mTORc2 isn't a switch, it is some kind of gradient just like the putative 50% mTOR1 suppression at 5mg raising 10%ish per mg. 

 

Long term edge riding is not necessarily safe from some level of mTOR1c interference nor would it effect everyone the same. We should not be afraid to discuss the serious consequences if you get it wrong, especially for "younger" people.

 

Further, cataracts and testicular degeneration are no joke (we've already had people report eye issues and reduce sex drive here); and people with autoimmune issues can also get triggered by the immune boost. Finally just because it piles on everything, covid can raise antinuclear antibodies (possible the source of long covid), as can age, so there may be more of us with mild autoimmune issues than we know.

 

​I've been following your high on / long off regimen with great interest since the body handles acute insults much better than chronic ones. Your noticing that effects lasted long after the dose had cleared tracks with some of the single dose papers. Have you had an ANA blood test and if so, have there been any changes?

 

I'm wondering if rapamycin does an ISR reset similar to ISRIB and possible quercetin. (I won't go into it but very exciting work: Drug Reverses Age-Related Mental Decline Within Days - UCSF)

 

The last study is Rifampicin not Rapamycin (don't mix the two - sorry for the typo) but should be of interest to some one with cognitive issues, like say PA. 

 

As for Metformin (aka Goat's rue if you can't get it otherwise) again, please actually read what I said before going off.

 

I never said Metformin would "ameliorate" anything in the first two studies. What I said was: "Metformin does seem to be synergetic (I'd love to see a test of rapamycin and berberine) and help with glucose rise from side effect level dosing."

[DJSwarm]

Speaking of rapamycin and berberine... looks like they synergistically inhibit mTOR1, possible allowing for lower doses of rapamycin to be effective. I'd recommend caution mixing the two: Berberine sensitizes rapamycin‑mediated human hepatoma cell death in vitro 

 

Recent research has demonstrated that berberine has anticancer activity against various types of cancer, mediated through the suppression of mammalian target of rapamycin (mTOR). The present study aimed to investigate the in vitro synergistic anticancer effect of combined treatment of rapamycin at various concentrations (0, 10, 50, 100 and 200 nM) and berberine (62.5 µM) in SMMC7721 and HepG2 hepatocellular carcinoma (HCC) cell lines, and the potential underlying molecular mechanism. The combined use of rapamycin and berberine was found to have a synergistic cytotoxic effect, with berberine observed to maintain the cyotoxic effect of rapamycin on HCC cells at a lower rapamycin concentration. Moreover, the cells treated with the combination of the two agents exhibited significantly decreased protein levels of phosphorylated (p)‑p70S6 kinase 1 (Thr389), the downstream effector of mTOR, compared with the cells treated with rapamycin or berberine alone. Furthermore, overexpression of cluster of differentiation (CD) 147, a transmembrance glycoprotein associated with the anticancer effects of berberine, was found to upregulate p‑mTOR expression and inhibit cell death in SMMC7721 cells co‑treated with rapamycin and berberine. In conclusion, the findings of the present study suggest that the combined use of rapamycin and berberine may improve HCC therapy through synergistically inhibiting the mTOR signaling pathway, which is at least in part, mediated through CD147.

 

Looks like berberine maybe a cheaper and safer mTOR1 inhibitor all on its own: Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression  BBR extended the lifespan of chemotherapy-treated mice and naturally aged mice by ~52% and ~16.49%, respectively. The residual lifespan of the naturally aged mice was extended by 80%, from 85.5 days to 154 days. The oral administration of BBR in mice resulted in significantly improved health span, fur density, and behavioral activity. Therefore, BBR may be an ideal candidate for the development of an anti-aging medicine.  

 

Who knew? More fun reading Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway ("...new insight into berberine’s molecular mechanism and its therapeutic potential in the treatment of atherosclerosis.)  Berberine Induces Autophagic Cell Death in Acute Lymphoblastic Leukemia by Inactivating AKT/mTORC1 Signaling (We find BBR caused ALL (Acute Lymphoblastic Leukemia) cell death by inducing autophagy. We also investigate the underlying mechanism responsible for BBR-induced autophagy. The findings will provide crucial insight into the application of BBR on ALL treatment.)

 

Looks like probably liposomal berberine is needed to improve absorption, or, maybe just the right microbiome: Transforming berberine into its intestine-absorbable form by the gut microbiota; or, if you have a lab; d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble form of vitamin E and is comprised of a hydrophilic polar head and a lipophilic alkyl tail resulting in amphiphilic properties for improving bioavailability.

 

If anyone tests this (R+BBR), please report back.

 

 

[judge]

Excellent info, love the Vit E info!  Thanks!

Speaking of rapamycin and berberine... looks like they synergistically inhibit mTOR1, possible allowing for lower doses of rapamycin to be effective. I'd recommend caution mixing the two: Berberine sensitizes rapamycin‑mediated human hepatoma cell death in vitro 

 

Recent research has demonstrated that berberine has anticancer activity against various types of cancer, mediated through the suppression of mammalian target of rapamycin (mTOR). The present study aimed to investigate the in vitro synergistic anticancer effect of combined treatment of rapamycin at various concentrations (0, 10, 50, 100 and 200 nM) and berberine (62.5 µM) in SMMC7721 and HepG2 hepatocellular carcinoma (HCC) cell lines, and the potential underlying molecular mechanism. The combined use of rapamycin and berberine was found to have a synergistic cytotoxic effect, with berberine observed to maintain the cyotoxic effect of rapamycin on HCC cells at a lower rapamycin concentration. Moreover, the cells treated with the combination of the two agents exhibited significantly decreased protein levels of phosphorylated (p)‑p70S6 kinase 1 (Thr389), the downstream effector of mTOR, compared with the cells treated with rapamycin or berberine alone. Furthermore, overexpression of cluster of differentiation (CD) 147, a transmembrance glycoprotein associated with the anticancer effects of berberine, was found to upregulate p‑mTOR expression and inhibit cell death in SMMC7721 cells co‑treated with rapamycin and berberine. In conclusion, the findings of the present study suggest that the combined use of rapamycin and berberine may improve HCC therapy through synergistically inhibiting the mTOR signaling pathway, which is at least in part, mediated through CD147.

 

Looks like berberine maybe a cheaper and safer mTOR1 inhibitor all on its own: Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression  BBR extended the lifespan of chemotherapy-treated mice and naturally aged mice by ~52% and ~16.49%, respectively. The residual lifespan of the naturally aged mice was extended by 80%, from 85.5 days to 154 days. The oral administration of BBR in mice resulted in significantly improved health span, fur density, and behavioral activity. Therefore, BBR may be an ideal candidate for the development of an anti-aging medicine.  

 

Who knew? More fun reading Berberine alleviates ox-LDL induced inflammatory factors by up-regulation of autophagy via AMPK/mTOR signaling pathway ("...new insight into berberine’s molecular mechanism and its therapeutic potential in the treatment of atherosclerosis.)  Berberine Induces Autophagic Cell Death in Acute Lymphoblastic Leukemia by Inactivating AKT/mTORC1 Signaling (We find BBR caused ALL (Acute Lymphoblastic Leukemia) cell death by inducing autophagy. We also investigate the underlying mechanism responsible for BBR-induced autophagy. The findings will provide crucial insight into the application of BBR on ALL treatment.)

 

Looks like probably liposomal berberine is needed to improve absorption, or, maybe just the right microbiome: Transforming berberine into its intestine-absorbable form by the gut microbiota; or, if you have a lab; d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS) is a water-soluble form of vitamin E and is comprised of a hydrophilic polar head and a lipophilic alkyl tail resulting in amphiphilic properties for improving bioavailability.

 

If anyone tests this (R+BBR), please report back.

 

[timedilation]

I have been following this thread for several years and have been taking rapamycin too.

 

I have a clinically diagnosed mitochondrial defect -- seemingly due to a PINK1 and OPA1 mutation -- which is disabling.

 

Sirolimus was a miracle drug for about 3 years -- i was super productive with my behavioral genetics research -- but the efficacy dissipated.

 

Do you get the impression that rapamycin would help these kinds of mitochondrial disorders (at least temporarily) for people of all ages, or would you expect the benefits to be mainly limited to older people?

[bhangchai]

"A research group at the Max Planck Institute for Biology of Ageing in Cologne, Germany, has now shown in laboratory animals that brief exposure to rapamycin has the same positive effects as lifelong treatment opening new doors for a potential application in humans."

 

 

Exploring the brief use of rapamycin treatment in early adulthood to extend lifespan

<https://medicalxpres...bOtnYqucEB2bKA>

 

 

Original article at:

 

www.nature.com/articles/s43587-022-00278-w

[illerrre]

If you're seemingly healthy, at 35, how would you go about Rapamycin in a safe way? 

 

I'm devouring as much information as I can, but it's difficult. 

 

Somehow from all the reading, it seems like 5mg per week for maybe 4 weeks straight once per year might be a good dose to get some benefits while not risking side effects?