955 replies to this topic

[to age or not to age]

 

 

A Doctor Alan Green posted this on the Aging Matters Blog in the comments section.

 

I take Rapamycin 6 mg a week for past 6 months. (cost $ 4.00) for 1 mg from Canada. I also include Metformin 500mg daily, exercise and diet. I have had no side effects. The improvement in cardiovascular function has been extraordinarily good. My weight has gone from 170 to 150 and waist line from 38 inches to 33. After ! year if my results continue as good as seems, I intend to prescribe Rapamycin off label for middle age persons who make proper informed consent. I am 73.

I emailed back and forth with Dr Green. The problem with doctors prescribing rapamycin that I have encountered is that they immediately (and I'm talking relatives who are MDs and MDs I actually know) google the side effects; being unfamiliar with the drug, and read a possible horror story including losing their license and looming malpractice suits.

We may opt for China.   

 

 

Here's a link to the aforementioned blog:  http://joshmitteldor...apamycin-redux/

 

 

[to age or not to age]

My reply in the above box should have been a separate box.   It actually should start at "I emailed back and forth with Dr. Green...

[Jaris]

"I emailed back and forth with Dr Green. The problem with doctors prescribing rapamycin that I have encountered is that they immediately (and I'm talking relatives who are MDs and MDs I actually know) google the side effects; being unfamiliar with the drug, and read a possible horror story including losing their license and looming malpractice suits.

We may opt for China. "

 

This is exactly right. I've talked to 2 MDs that I know, as well as emailed Dr Green several times. Dr Green is the only one who would consider giving me a prescription, and only if I was his patient and came to his office regularly. I live in CA and he's on the East coast, so I'm not sure if that will happen. Everyone should always be aware of the potential side affects of anything they take. For Rapamycin, they aren't trivial; type 2 diabetes, cancer, serious infections, etc. Everyone has to do their own investigation and perhaps wait for more studies on humans using lower doses and/or longer periods between doses.

 

I have an ulterior motive which makes it more attractive to me personally, but everyone needs to make their own decision based on risk/reward. The problem (IMHO) is that doctors don't always know the facts about the drugs they prescribe, leading to avoidable illnesses, which they are often sued for, which means that someone like me who is aware of and wants to take on the risk can't find a local doctor to let me do it. (Rant complete.)

[Ebayasianf]

Jarvis,
I joined this website specifically to find Rapamycin for my aging dog, so I'm in to buying some from you..BUT reading the replies to your request, I just want to be sure you are buying a quality product. Also the dosing for dogs seem o be .1mg and I want to be sure there is a way to get that measurement when dosing my dog. I think the studies say 3 times a week, but my dog is only 10 pounds so I would do just once a week. Finally, there are other names for the drug. Perhaps we should contact that doctor who is already buying and taking the drug, Dr. Alan Green. What do you think? I'm so new here I can't even find the aging matters blog to contact Dr. Alan Green.

[Jaris]

First, here's the link to the blog: http://joshmitteldor...apamycin-redux/

It's a very long discussion, so you might just want to search within it for "Green".

Rapamycin is also known as Sirolimus (generic) and Rapamune (Pfizer's brand name). There are 2 other names for another drug company's knock-offs, but they are expensive. Dr Green takes Sirolimus ($4-6 per 1mg pill from Canada) but you need a prescription.

 

Second, you bring up a good point about being able to measure 0.1 mg. That would not be easy. I've found inexpensive scales that measure down to 1mg, but in fact that only means that it's accurate to 1mg. You can't calibrate a scale more precisely than it can detect, and also the rounding error must be taken into account. So if you assume the scale displays "1mg" from, say 0.51mg (actual) to 1.49mg (actual), then you can see that you can never be assured of a precision any better than half a mg either way  (and, in fact, it's worse than that). This is just one problem with measuring out such small doses yourself.

 

If you are looking to measure down to 0.1mg then you need a scale that can measure down to that amount, or better yet to 0.05mg. Such a scale is very specialized and is generally sold to labs. They are very sensitive to things like local gravitational variance, humidity and temperature. I haven't found one that costs less than several hundred dollars. If you do, please let me know. Here's an example from ebay: http://www.ebay.com/...w8AAOSwnbZYEE8i

 

Third, I am far from being able to assure myself - or anyone else - that what I may (or may not) receive from China is a "quality product". I don't know how important this is to you, but we might discuss sharing the cost of having a sample tested. Let me know. if that is a possibility.

Edited by Jaris, 21 November 2016 - 02:29 AM.

[APBT]

Not to steer this too far off the original topic, but here's a link regarding Rapamycin and dogs:

http://dogagingproject.com/
 

[APBT]

"I emailed back and forth with Dr Green. The problem with doctors prescribing rapamycin that I have encountered is that they immediately (and I'm talking relatives who are MDs and MDs I actually know) google the side effects; being unfamiliar with the drug, and read a possible horror story including losing their license and looming malpractice suits.

We may opt for China. "

 

This is exactly right. I've talked to 2 MDs that I know, as well as emailed Dr Green several times. Dr Green is the only one who would consider giving me a prescription, and only if I was his patient and came to his office regularly. I live in CA and he's on the East coast, so I'm not sure if that will happen. Everyone should always be aware of the potential side affects of anything they take. For Rapamycin, they aren't trivial; type 2 diabetes, cancer, serious infections, etc. Everyone has to do their own investigation and perhaps wait for more studies on humans using lower doses and/or longer periods between doses.

 

I have an ulterior motive which makes it more attractive to me personally, but everyone needs to make their own decision based on risk/reward. The problem (IMHO) is that doctors don't always know the facts about the drugs they prescribe, leading to avoidable illnesses, which they are often sued for, which means that someone like me who is aware of and wants to take on the risk can't find a local doctor to let me do it. (Rant complete.)

 

You may try this as a potential source for a prescribing MD in your area:  http://www.a4m.com/directory.html

[VP.]

Question from Reddit: "Where can I get Rapamycin without an Rx" 

Interesting answers. 

https://www.reddit.c...cin_without_rx/

 

[DareDevil]

This is interesting. If I understood correctly one can supplement .25mg of Rapamycine with grapefruit juice for increased bioavailability and get the same effect as 1mg which makes a $400 bottle of 100 x 1mg last a full year. I am toying with the idea of getting some from Turkey. From the above link:

https://www.reddit.c...cin_without_rx/

 

[–]AmadeusJpn 3 points

 

24 days ago

 

I live in Japan, and I imported Rapamune(Pfizer's trade mark for rapamycin) from Turkey. I paid about $420 for 1mg tablet x 100. I take 2mg of Rapa every week with grapefruit juice that increases the drug level in blood by 3.5 times. The only minor side effect is mouth sores.

If it is low dosage, there is almost no negative effects. 0.5 - 1.0 mg/day is low dosage. If you take rapamycin with grapefruit juice, 1mg a week is roughly equivalent to 0.5 a day dosage, since the juice increases the bioavilability by 350%.

This is interesting. If I understood correctly one can supplement .25mg of Rapamycine with grapefruit juice for increased bioavailability and get the same effect as 1mg which makes a $400 bottle of 100 x 1mg last a full year. I am toying with the idea of getting some from Turkey. From the above link:

https://www.reddit.c...cin_without_rx/

 

[–]AmadeusJpn 3 points

 

24 days ago

 

I live in Japan, and I imported Rapamune(Pfizer's trade mark for rapamycin) from Turkey. I paid about $420 for 1mg tablet x 100. I take 2mg of Rapa every week with grapefruit juice that increases the drug level in blood by 3.5 times. The only minor side effect is mouth sores.

If it is low dosage, there is almost no negative effects. 0.5 - 1.0 mg/day is low dosage. If you take rapamycin with grapefruit juice, 1mg a week is roughly equivalent to 0.5 a day dosage, since the juice increases the bioavilability by 350%.

[Jaris]

First, beware of the grapejuice claim. The study he points to only had high-dose cancer patients; 45-90 mg a week! Not guaranteed to have similar results for low-doses. However, the fact that the writer was noticing mouth sores taking just 2mg/week may indicate that the dose is multiplied as he suggests (and possibly even more, which worries me). If so, I think he may be taking too much. I think 1mg/week might be better.

 

Second: I've chased down this lead too. I asked the guy from Japan (quoted in the reddit discussion) for his source. I contacted his source, who said that they only sell to customers in Japan, but sent me to a similar contact for USA. That contact said "sorry, you have to have a prescription". Finally, through yet another lead, I discoverer someone on Reddit who is in India and would sell it to me. If anyone would like his contact info, send me a PM. Here's his price:

 

Product: 200 Sirolimus (1mg)

Price: $600.00

Edited by Jaris, 08 December 2016 - 01:24 AM.

[DareDevil]

Hi Jaris,

 

Thanks for hunting this down. It is 25% cheaper than the source in Turkey although you must buy double the amount. 200 tablets are enough for two years maybe making it plausible as a youthening substance. I'd much appreciate his coordinates by PM as I am definitely seeking to try this. 

 

DareDevil

[DareDevil]

It might also be advisable to reduce risks by taking rapamycin in a "transient treatment"?

 

https://elifescience...ontent/5/e16351

 

In mice 3 months treatment was sufficient to dramatically increase lifespan. Then again taking longer term microdoses may be wiser. Dosing this stuff is going to be trial and error, with hopefully no serious consequences for the errors.

 

DareDevil

[Jaris]

Yes, best dose will for now have to be discovered via trial and error.

 

There seems to be some initial guidance, but not much. It's been reported (via an old interview of someone who knew him) that the discoverer of Rapamycine took 1mg/day for several years. Currently Dr Green (in NY) is having good results taking 6mg once per week (for over a year now). He told me that he was taking a larger dose just to see if he had any side affects (as of last month - none). Someone who lives in Japan mentioned on Reddit that he is taking 2mg/week but (he believes) is increasing bio-availability 350% by also drinking grapefruit juice. He's had mouth sores as a side affect. My own gut feeling: I think both Dr Green and our Japanese friend are both overdosing slightly. That's all of the applicable info from actual selfexperimentalists (which should be a word!) that I know about. Please add anything else you've heard.

[VP.]

From the Economist:

Alexander Zhavoronkov, the boss of Insilico Medicine, a longevity firm, says he is testing rapamycin on himself (self experimentation does not seem uncommon in the field). But he warns it is necessary to have a significant knowledge of biomedicine to do so safely. The drug has serious side effects; rodents treated with it suffer from insulin resistance and it suppresses the immune system. That’s good when preventing the rejection of organ transplants—the drug’s current medical use—but not so good in otherwise healthy people. One idea is that low doses might preserve the drug’s benefits while limiting its side-effects.

 http://www.economist...-up-adding-ages

Alexander has a very active Facebook page. Maybe someone can just ask him about dosing? Preferably a Scientist.

 

[Aardvark202]

A study earlier this year suggested that either intermittent dosing of rapamycin was necessary to avoid side effects, and/or the alternative use of mTORC1 specific inhibitor Everolimus (a rapamycin analogue).  Most studies have shown that mTORC2 inhibition is responsible for the negative effects on glucose tolerance seen with rapamycin, though high does Everolimus also has significant side effects.

 

https://www.ncbi.nlm...pubmed/26463117 Arriola Apelo SI et al"Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system." Aging Cell, Feb 2016.

 

Personally I'm only 26 so i'll likely wait awhile for research to advance before considering intermittent Rapamycin as a treatment.

 

 

[Aardvark202]

On an additional note, I was wondering if anyone here knows why rapamycin is more effective for lifespan extension then metformin when they are both mTORC1 inhibitors?

 

https://www.ncbi.nlm...pubmed/27984722 Wu et al, "An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer." Cell, Dec 2016

 

Is it a matter of rapamycin being a more powerful inhibitor?  Or, alternatively, is it an off-target effect that helps rapamycin's case? I know it has also been shown to reduce progerin levels in progeria patients, but I don't know if this is dependent on mTORC inhibition or not.

 

 

Edited by McSchwangstasis, 19 December 2016 - 02:47 PM.

[VP.]

• What is the difference between rapamycin and metformin? Listen to Tim Ferriss's podcast at time [50:23] 
• http://fourhourworkw...-easter-island/

[Jaris]

Interesting podcast. Having lived and worked in the Silicon Valley for 10 years, I'm not at all surprised that there are several (many?) self-experimenters here, and that they are experimenting with Metformin and Rapamycin.

Another thing I learned from the podcast was the idea that the reason Rapamycin might work so well taken intermittently is that it causes the cells to, basically, take out the garbage briefly, but then go back to re-building. You need both.

With that in mind, I'm going to take 2 mg of Rapamycin (possibly with 6-8 oz of grapefruit juice to increase bio-availability) then skip 6 days. I'm also planning to take the following supplements to help cells rebuild.

 

(A lot of the following is probably not supported  by studies, but is also not too far fetched. You probably know most if not all of this.)

 

Liposomal Glutathion

Cleanses the brain at the cellular level. Antioxidant and detoxification functions. The liposomal delivery system bypasses the digestive process and is instead directly absorbed.

 

Nicotinamide Riboside

Optimizes NAD+ levels and sirtuin function in cells to support their most critical metabolic processes like cellular detoxification, DNA repair and energy production.

 

Hydroxycitric Acid (HCA) 

Protects mitochondria & reduces inflammation.

 

PQQ

Activates cell signaling pathways that have the potential to reverse cellular aging.

Promotes growth of new mitochondria within aging cells, up-regulates cellular metabolism, protects neurons, and repairs DNA.

 

QH

The reduced, active, antioxidant form of Co-Q10, which is significantly better absorbed than ubiquinol.

PQQ with QH promotes the creation of new mitochondria, a process known as mitochondrial bio-genesis. Supports both heart health and cognitive function.

 

That's my plan. It starts as soon as my rapamycin arrives. Any day now.

 

[VP.]

“We think this could provide a paradigm shift in the treatment of age-related disease, including cancer,” said Buck professor Judith Campisi, PhD, senior scientist on the study. “Imagine the possibility of taking a pill for a few days or weeks every few years, as opposed to taking something with side effects every day for the rest of your life. It’s a new way of looking at how we could deal with age-related maladies.”

 

http://www.buckinsti...ging-and-cancer

[tintinet]

Thinking of starting rapamycin also. Listed from some Canadian on line pharmacies. Not cheap, but a little should go a long way at least.

[saj87]

I have read it is being tested for Alzheimers and that it reduces amyloid-beta among other things. As far as I read (or understood) the mice were fed rapamycin, I wonder what is the source they are getting rapamycin from. Anyone knows?

[tintinet]

I have read it is being tested for Alzheimers and that it reduces amyloid-beta among other things. As far as I read (or understood) the mice were fed rapamycin, I wonder what is the source they are getting rapamycin from. Anyone knows?

Rapamycin was purchased from TCI Chemicals (India) Pvt. Ltd., India.

Mol Neurobiol. 2016 Sep 22. [Epub ahead of print]
Neuroprotection Through Rapamycin-Induced Activation of Autophagy and PI3K/Akt1/mTOR/CREB Signaling Against Amyloid-β-Induced Oxidative Stress, Synaptic/Neurotransmission Dysfunction, and Neurodegeneration in Adult Rats.
Singh AK1, Kashyap MP2, Tripathi VK3, Singh S1, Garg G1, Rizvi SI4.

[Kenbar]

Article from March 2012:

 

"You don’t have to go far to find supposed ways of delaying the ageing process, from oddball diets to special supplements. But these fountains of youth are all hype and no substance. For now, there are only a few methods that have consistently extended the lives of mammals. Eating less – formally known as “caloric restriction” – is one of these. Rapamycin, a drug originally found in Easter Island bacteria, is another. It can lengthen the lives of old mice by 9 to 14 per cent, and it boosts longevity in flies and yeast too.

 

"But rapamycin has its downsides. For a start, it strongly suppresses the immune system. That is why it is currently given to people who receive new organs, to stop them from rejecting their transplants. Rapamycin can also increase the risk of diabetes. In mice, rats and humans, the drug weakens the ability to stabilise levels of sugar in the blood. Individuals who take it for a long time become resistant to insulin, and intolerant to sugar.

 

"You’d expect the opposite. Longer-lived animals ought to be better at dealing with sugar, and less likely to suffer from insulin resistance. Indeed, that’s what you see in individuals that cut down on calories. So why does rapamycin behave so paradoxically?

 

Much more... http://blogs.discove...s/#.WGA9EFUrK01

Edited by Kenbar, 25 December 2016 - 09:45 PM.

[saj87]

Article from March 2012:

 

"You don’t have to go far to find supposed ways of delaying the ageing process, from oddball diets to special supplements. But these fountains of youth are all hype and no substance. For now, there are only a few methods that have consistently extended the lives of mammals. Eating less – formally known as “caloric restriction” – is one of these. Rapamycin, a drug originally found in Easter Island bacteria, is another. It can lengthen the lives of old mice by 9 to 14 per cent, and it boosts longevity in flies and yeast too.

 

"But rapamycin has its downsides. For a start, it strongly suppresses the immune system. That is why it is currently given to people who receive new organs, to stop them from rejecting their transplants. Rapamycin can also increase the risk of diabetes. In mice, rats and humans, the drug weakens the ability to stabilise levels of sugar in the blood. Individuals who take it for a long time become resistant to insulin, and intolerant to sugar.

 

"You’d expect the opposite. Longer-lived animals ought to be better at dealing with sugar, and less likely to suffer from insulin resistance. Indeed, that’s what you see in individuals that cut down on calories. So why does rapamycin behave so paradoxically?

 

Much more... http://blogs.discove...s/#.WGA9EFUrK01

 

Interesting. If what you say is exactly like that I would like to see an answer to that.

[tintinet]

http://www.kurzweila...isking-diabetes

[Kenbar]

http://www.kurzweila...isking-diabetes

 

Combining it with Metformin. Metformin by itself holds the possibility of a little life extension. Perhaps combining the two might up the anty some more while reducing the diabetic risk...but then "there would still be that pesky immune suppression to deal with".

 

Personally I think I will sit this one out for the time being. Playing with c60oo and cycloastragenol...maybe Ta-65 is about the limit of my daringness for the moment. Definitely will keep my eyes on Rapamycin and Metformin though. See where that goes.

Edited by Kenbar, 26 December 2016 - 04:47 AM.

[saj87]

 

http://www.kurzweila...isking-diabetes

 

Combining it with Metformin. Metformin by itself hold the possibility of a little life extension. Perhaps combining the two might up the anty some more while reducing the diabetic risk...but then "there would still be that pesky immune suppression to deal with".

 

Personally I think I will sit this one out for the time being. Playing with c60oo and cycloastragenol...maybe Ta-65 is about the limit of my daringness for the moment. Definitely will keep my eyes on Rapamycin and Metformin though. See where that goes.

 

 

Would rapmy + ergoloid be a good stack?

[Kenbar]

 

 

http://www.kurzweila...isking-diabetes

 
Combining it with Metformin. Metformin by itself hold the possibility of a little life extension.

 

 
Would rapmy + ergoloid be a good stack?

 

 
 
Sorry but I'm not knowledgeable enough to even start to answer that. I did take a look here.... https://en.wikipedia.../wiki/Ergoloid 
 
This raises some small alarms:
 
"Despite the fact that hydergine has been used in the treatment of dementia for many years, its mechanism of action is still not clear.
 
"Adverse effects are minimal. The most common include transient, dose dependent nausea and gastrointestinal disturbances,^%5B5%5D and sublingual irritation with SL tablets. Other common side effects include:^{%5B9%5D%5B10%5D}

• Cardiovascular: orthostatic hypotension, bradycardia
• Dermatologic: skin rash, flushing
• Ocular: blurred vision
• Respiratory: nasal congestion
• Increased risk of fibrosis and ergotism.^{%5B11%5D%5B12%5D}

As a result of the last-mentioned effects, the use of ergot derivatives for the treatment of blood circulation disorders, memory problems, sensation problems and the treatment of migraine is no longer permitted in some EU countries because the risks are believed to outweigh any benefits.^{%5B11%5D
 
Perhaps some other more knowledgeable member will chime in with their thoughts.}

Edited by Michael, 30 June 2017 - 06:51 PM.
trim quote

[Jaris]

Metformin is something that i'm thinking of combining  with rapamyciin because I've seen similar studies. Thanks for the link. 

 

Much of the "common wisdom" about rapamycin is derived from experience with cancer and transplant patients who take much, MUCH larger doses than we have been discussing here. Dosing is everything.

One example of this; some say that it suppresses our immune systems, thereby leaving us open to more dangerous infections. But at least one study demonstrated that at lower, intermittent doses, its affect is to focus the immune system onto real targets. Instead of reducing the immune response, it adjusts it to recognize threats more accurately. This is sparking early discussions about how it might benefit those with auto-immune diseases.

Edited by Jaris, 26 December 2016 - 07:25 AM.

[tintinet]

Hopefully the dog study will shed some light on this.

http://www.cnn.com/2...nger/index.html