955 replies to this topic

[Kenbar]

Looking at the cost of Rapamycin...looks very pricey. Also I do not see it as an option from Canada, not without a prescription anyways. Price and availability might be two big roadblocks. Metformin is available from Canada without a prescription, as far as I can tell.

Edited by Kenbar, 26 December 2016 - 02:22 PM.

[Diocletian]

Is anyone currently working on drug that have Rapamycin+Metformin anti aging benefits but without side effects?

[Jaris]

I don't believe that metformin is available to USA from Canada w/o a prescription; it is a prescribed drug in the USA, . However, metformin is a widely prescribed drug with very few side affects and it was not hard to convince my doctor to prescribe it for me.

Rapamycin - usually in the form of sirolimus pills - is another story. There are doctors who are friendly towards those of us wanting to experiment. But even they might be resistant due to the serious side affects seen at high doses; they may need to be educated about the difference in dosage levels (about 3.5mg a week vs up to 90mg a DAY for cancer patients).

 

If by "pricey" you mean less than $1 a day, then yeah. But to most that's reasonable.

Again, it comes back to dosing.

You can get 1mg sirolimus pills from Canada for $6 each ($3 each from India). At the low and intermittent doses we're talking about here, you might want to take 1 pill a week. That's a very low dose, but might be enough to see benefits.

If you want a higher dose and more bang for your buck, there's a trick that improves the bio-availability by $350%. By drinking grapefruit juice with the pill, and taking just one 1mg pill a week, you end up getting (on average) the equivalent of 0.5mg a day (3.5mg averaged over over 7 days). Which is at the level that's often suggested. But, again, you want "intermittent " dosing, which means (for example) one dose once a week. It might end up being bettter to take a dose every month or every 3 months etc. We just don't know yet.

The grapefruit trick was studied and verified via a study of cancer patients who often take 45-90mg a day. It might work differently when taking much smaller doses.

One doctor who is self-experimenting takes 6mg once a week (and is also taking metformin). When I asked him why so much (almost twice what's being suggested elsewhere), he said he wanted to see if he experienced side affects at the 6mg/week dose. He hasn't but he also does not recommend taking as much as he is.

 

So it can be done on $6 per week. The prescription problem is something I'm working on.

Edited by Jaris, 26 December 2016 - 08:09 PM.

[Jaris]

Is anyone currently working on drug that have Rapamycin+Metformin anti aging benefits but without side effects?

Everolimus, a.k.a. RAD001, is a chemical cousin of rapamycin, a.k.a. Sirolimus, that is used similarly to prevent tissue rejection. I believe a recent mouse study showed that it had fewer MTOR2 related side affects. I'll try to find the reference and post it later.

It's probably very expensive and therefore a good bet that others are working on it as well.

Rapamycin aka Sirolimus is no longer covered by patents, so it is much less expensive.

[Kenbar]

Metformin seems to be available from Canada. I order Retin-A  cream from this site, without a prescription to keep my acne at bay (and it works well). But I do not see Rapamycin on their site.

 

http://canadian-phar...tformin&cur=USD

[tintinet]

Some options here with prescription:

https://www.pharmacy...sirolimus/1 mg/

[Kenbar]

Some options here with prescription:

https://www.pharmacy...sirolimus/1 mg/

 

Might be able to order from here, one from your link, without a prescription https://www.canadaph...e=Rapamune2555 

 

But the cheapest for the generic (shipped from India) is still $359 for 100...1mg. So if I was to take one of these low dose pills every day...add 500mg of Metformin every day as well...close to $400 for a 3 month supply. So around $133 per month. I already spend around $200+ each month on various things. C60oo, Astragaloside IV, Cycloastragenol...and a whole bunch of other things. So that would push me up to well over $300 per month unless I'm missing the concept, dosing ect...of the Metformin/Rapamycin combo. And the depressed immune system issue might still be a lingering possible side effect from what I have read. 

 

Edited by Kenbar, 26 December 2016 - 11:39 PM.

[Kenbar]

Link did not work...a retry. https://www.canadaph...me=Rapamune2555

[Jaris]

 

Some options here with prescription:

https://www.pharmacy...sirolimus/1 mg/

 

Might be able to order from here, one from your link, without a prescription https://www.canadaph...e=Rapamune2555 

 

But the cheapest for the generic (shipped from India) is still $359 for 100...1mg. So if I was to take one of these low dose pills every day...add 500mg of Metformin every day as well...close to $400 for a 3 month supply. So around $133 per month. I already spend around $200+ each month on various things. C60oo, Astragaloside IV, Cycloastragenol...and a whole bunch of other things. So that would push me up to well over $300 per month unless I'm missing the concept, dosing ect...of the Metformin/Rapamycin combo. And the depressed immune system issue might still be a lingering possible side effect from what I have read. 

I plan to take a low dose with grapefruit juice once a WEEK. 100 pills would last me almost 2 years, or about $14.50 a month.

What have you read that suggests that low dose intermittent use may cause serious side effects? Of course it's possible - not saying there is no risk.

 

thanks for the link, but you get to the end and they still require a script.

From their FAQ:

 

Q2: Do I need a prescription to order from your company?

A: Yes. Like your local pharmacy, Canada Pharmacy Online requires a valid prescription written by a licensed physician, in order for us to dispense your prescription medications. All prescription medications are clearly marked by . Without a valid prescription for such items, we will not be able to process and ship your order. 

Edited by Jaris, 27 December 2016 - 01:05 AM.

[Kenbar]

 

 

Some options here with prescription:

https://www.pharmacy...sirolimus/1 mg/

 

Might be able to order from here, one from your link, without a prescription https://www.canadaph...e=Rapamune2555 

 

But the cheapest for the generic (shipped from India) is still $359 for 100...1mg. [...]

I plan to take a low dose with grapefruit juice once a WEEK. 100 pills would last me almost 2 years, or about $14.50 a month. [...]

 

I have not read anything regarding doses. Seems like your plan would be very conservative. A safe approach. But...do you think such a plan would yield much in the way of life extension?

Edited by Michael, 30 June 2017 - 06:54 PM.
trim quotes

[Jaris]

Well, i'm not trying tosell you anything; just trying to share info,, so don't make me work so hard!

There have been recent studies that suggest a once-a-week low-dose approach is a way to access some of the benefits while avoiding the side effects. They've been mentioned in this topic before. There is some logic to this apparent madness.

BTW: The doctor I referred to earlier, who is taking a 6mg dose once a week, would be willing to give me a prescription, but I would have to travel to NY from CA so he could examine me first. So that might be an option for anyone living close to him.

[Kenbar]

I found this...

 

"Getting the dose correct is another problem. A normal human dose of rapamycin is between 2 and 5 milligrams per day, much lower than the dose given to the mice, which was 2.24 milligrams per kilogram of body weight per day.

 

http://www.nature.co...s.2009.648.html

 

A 200 pound person = 90 kilograms. So to equal the life extending rat test...a 200 pound man would need 90 X 2.24...= 201.6 mg per day.. That's 1411 mg per week...and you would be taking...1 mg per week vs the 1411 mg. 

 

So if this info and math is correct I can see where it would be a safe play. But I question if it would be an effective amount to attain your life extensin goal. For me it would be difficult to even try it as I do not know the right doctor...my doctor is a by the book kind of guy...so unless I have a transplant of some sort...think I am out of luck for now. 

 

Metformin is in human trials right now as an anti aging drug. Not sure when the trials will end and the results made public.

 

http://wjbf.com/2015...g-human-trials/

 

 

 

 

Edited by Kenbar, 27 December 2016 - 02:30 AM.

[Jaris]

Well then, it's a good thing we're not ginormous mice! 

 

Seriously though, here are a few things to consider:

1. We aren't mice, and the kind of estimation in the previous post is very dangerous. Personally, I would not attempt to take more than 0.5 mg a day (averaged over a week) unless it was to treat cancer or keep a transplanted organ alive.
2. Rapamycin is a very powerful drug. Taken in huge, daily doses by patients who would surely otherwise die, it has very serious potential side effects. These include cancer and brain infections.
3. So the early studies were testing huge doses on mice to study this reality. Subsequent studies, exploring much lower and intermittent doses have been performed, giving us better info on dosing. Newer studies will give us an even better idea of the best dose for humans.

In theory, Rapamycin in low intermittent doses works very differently than what we've become familiar with. The idea behind most supplements is to replace - on a relatively massive daily basis - that which our bodies produced at a younger age, but no longer do. An analogy might be driving a car with a leaky transmission and adding transmission fluid every day. It keeps you going forward for now, but your transmission is  still going bad.

 

The idea behind intermittent low-dose Rapamycin therapy is fundamentally different. It's triggering the same pathways as caloric-restriction does. Think of taking a small dose once a week as fasting for a few days. Using the leaky transmission analogy; it shifts your cells into a recovery state, so that they can clear themselves of damaged parts and make way for repairs and new growth. You don't want them doing that constantly, because you want new growth too, so you do it once a week. To quote from this link: http://www.kurzweila...isking-diabetes

 

* In recent years it was also observed that it can function as a metabolic “signaler” that inhibits a biological pathway found in almost all higher life forms — the ability to sense when food has been eaten, energy is available and it’s okay for cell proliferation, protein synthesis and growth to proceed.

Called mTOR in mammals, for the term “mammalian target of rapamycin,” this pathway has a critical evolutionary value — it helps an organism avoid too much cellular expansion and growth when energy supplies are insufficient. That helps explain why some form of the pathway has been conserved across such a multitude of species, from yeast to fish to humans.

Age-related diseases include many of the degenerative diseases that affect billions of people around the world and are among the leading causes of death: cardiovascular disease, diabetes, Alzheimer’s disease and cancer.

Edited by Jaris, 27 December 2016 - 07:24 PM.

[zorba990]

Will 1mg 1xweek interfere with muscle building for more than just that one day?

http://m.fasebj.org/...Abstracts/306.5

""Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced sensitivity to the postprandial rise in amino acids, particularly leucine (Leu). To elucidate the molecular mechanism by which Leu stimulates protein synthesis in neonatal muscle, overnight fasted 7-day-old piglets were treated with rapamycin (an inhibitor of mammalian target of rapamycin complex 1/mTORC1) for 1 h and then infused with Leu for 1 h. Fractional rates of protein synthesis and activation of signaling components lead to mRNA translation were determined. Rapamycin completely blocked Leu-induced muscle protein synthesis. Rapamycin markedly reduced raptor-mTOR association, an indicator of mTORC1 activation. Consequently, phosphorylation of mTOR, S6K1, and 4EBP1, and eIF4E·eIF4G complex abundance were decreased and eIF4E·4EBP1 complex abundance was increased. Rapamycin had no effect on the association of mTOR with rictor, a crucial component for mTORC2 activation. Neither Leu nor rapamycin affected the phosphorylation of AMPK, PKB, or TCS2, signaling components that reside upstream of mTOR. eEF2 phosphorylation was not affected by Leu or rapamycin, although current dogma indicates that eEF2 phosphorylation is mTOR-dependent. Taken together, these in vivo data suggest that Leu stimulates muscle protein synthesis by enhancing mTORC1 activation and its downstream effectors. NIH AR44474, USDA 58-6250-6-001"

[Kenbar]

Well then, it's a good thing we're not ginormous mice! 

 

Seriously though, here are a few things to consider:

1. We aren't mice, and the kind of estimation in the previous post is very dangerous. Do not attempt to ingest anything more than 1mg a day.
2. Rapamycin is a very powerful drug. Taken in huge, daily doses by patients who would surely otherwise die, it has very serious side effects.
3. So the early studies were testing huge doses on mice to study this reality. Subsequent tests, exploring much lower and intermittent doses (including 1 on elderly humans) have been performed.

In theory, Rapamycin in low intermittent doses works very differently than what we've become familiar with.

 

"Subsequent tests, exploring much lower and intermittent doses (including 1 on elderly humans) have been performed." Can you post a link to the tests on the elderly humans? Sounds intriguing.

Edited by Michael, 30 June 2017 - 07:02 PM.
trim quotes

[Jaris]

Sure, here's a link: https://www.research...e990e045b03.pdf

 

Here are two quotes about doses: 

"... one of three doses of oral RAD001: 0.5 mg daily, 5 mg weekly, or 20 mg weekly."

"... was relatively well tolerated, particularly the 0.5 mg daily and 5 mg weekly dosing regimens."

 

This study was testing the affect Everolimus (a patented cousin to rapamycin) would have on their immune response to a flu vaccine. It actually improved it.

Obviously, this falls short of proving that these low doses enhance longevity in humans. Unfortunately (in one sense), Rapamycin itself isn't covered by a patent, so fewer big studies are funded.

There are other studies that look at different aspects of low and intermediate dosing, but this is the one I know of on humans so far.

 

As I've said before, my plan is too take 1mg along with grapefruit juice to boost bio-availability by 350%. So, the equivalent of 3.5mg/week or 0.5/day.

After a few months I may increase the dose slightly, maybe by 50% to 5.25mg/week or 0.75mg/day.

On a purely anecdotal level, I am in contact with two self-experimenters. One is 70 years young, takes 6mg once weekly. The other is 48, taking 2mg with 8 oz of grapefruit juice, so about 7mg week. Both are doing well after 1 year. The only side effect is minor mouth sores reported by the 48 year old. When I asked the 70 year old why he was taking 6mg weekly (which seemed a little high to me) he said that he was a guinea pig and wanted to see if he experienced any side effects. He says that he's had none, but has had an increase in energy, feels great, and has lost several belt-sizes.

Edited by Jaris, 27 December 2016 - 09:31 PM.

[Kenbar]

"Subsequent tests, exploring much lower and intermittent doses (including 1 on elderly humans) have been performed." Can you post a link to the tests on the elderly humans? Sounds intriguing.

 
Never mind, think I found some links.... https://www.google.c...chrome&ie=UTF-8
 
Not able to find the dosing amounts.

Edited by Michael, 30 June 2017 - 07:05 PM.
trim quotes

[Kenbar]

Sure, here's a link: https://www.research...e990e045b03.pdf

 

Here are two quotes about doses: 

"... one of three doses of oral RAD001: 0.5 mg daily, 5 mg weekly, or 20 mg weekly."

"... was relatively well tolerated, particularly the 0.5 mg daily and 5 mg weekly dosing regimens."

 

This study was testing the affect Everolimus (a patented cousin to rapamycin) would have on their immune response to a flu vaccine. It actually improved it.

Obviously, this falls short of proving that these low doses enhance longevity in humans. Unfortunately (in one sense), Rapamycin itself isn't covered by a patent, so fewer big studies are funded.

There are other studies that look at different aspects of low and intermediate dosing, but this is the one I know of on humans so far.

 

As I've said before, my plan is too take 1mg along with grapefruit juice to boost bio-availability by 350%. So, the equivalent of 3.5mg/week or 0.5/day.

After a few months I may increase the dose slightly, maybe by 50% to 5.25mg/week or 0.75mg/day. 

 

Oh, thanks!

[Kenbar]

Sure, here's a link: https://www.research...e990e045b03.pdf

 

Here are two quotes about doses: 

"... one of three doses of oral RAD001: 0.5 mg daily, 5 mg weekly, or 20 mg weekly."

"... was relatively well tolerated, particularly the 0.5 mg daily and 5 mg weekly dosing regimens."

 

This study was testing the affect Everolimus (a patented cousin to rapamycin) would have on their immune response to a flu vaccine. It actually improved it.

Obviously, this falls short of proving that these low doses enhance longevity in humans. Unfortunately (in one sense), Rapamycin itself isn't covered by a patent, so fewer big studies are funded.

There are other studies that look at different aspects of low and intermediate dosing, but this is the one I know of on humans so far.

 

As I've said before, my plan is too take 1mg along with grapefruit juice to boost bio-availability by 350%. So, the equivalent of 3.5mg/week or 0.5/day.

After a few months I may increase the dose slightly, maybe by 50% to 5.25mg/week or 0.75mg/day.

On a purely anecdotal level, I am in contact with two self-experimenters. One is 70 years young, takes 6mg once weekly. The other is 48, taking 2mg with 8 oz of grapefruit juice, so about 7mg week. Both are doing well after 1 year. The only side effect is minor mouth sores reported by the 48 year old. When I asked the 70 year old why he was taking 6mg weekly (which seemed a little high to me) he said that he was a guinea pig and wanted to see if he experienced any side effects. He says that he's had none, but has had an increase in energy, feels great, and has lost several belt-sizes.

 

Wonder what the differences are between Everolimus and Rapamycin.. If Everolimus is safer in some way. If it is, it might be worth the extra $$$ as your plan involves using such small doses. And it appears to be effective at small dose levels.

 

 

Edited by Kenbar, 27 December 2016 - 09:42 PM.

[Jaris]

The intermittent dosing and using Everolimus instead have both been studied and compared.

Here's the link from a previous post: https://www.ncbi.nlm...pubmed/26463117

[Kenbar]

The intermittent dosing and using Everolimus instead have both been studied and compared.

Here's the link from a previous post: https://www.ncbi.nlm...pubmed/26463117

 

Any thoughts on how you might implement Metformin in to your plan? Maybe once a week as well...opposite...maybe 3 days after the  

Rapamycin? Or would you do both the same day maybe?

[Jaris]

I'll have to do more reading about Metformin. I have a prescription, but haven't started taking it yet.

The self-experimenting MD I'm in contact with takes 500mg every day. Which sounds like a lot compared to the 6mg of Sirolimus per week thhat he takes, but they work differently.

Rapamycin  can function as a metabolic “signaler” that inhibits a biological pathway. As I understand it, signaling doesn't use up the molecules, so it takes very little.

 

Just need to correct something I posted earlier: cancer patients sometimes take up to 90mg of Rapamycin (or similar drugs such as Everolimus) per WEEK (not per day as i said earlier).

 

The grapefruit trick was studied in order to help cancer patients who are taking large doses of several other potent drugs as well, causing digestion distress. Taking less by just drinking juice is a good thing. I'm a little concerned about extrapolating to much smaller doses: how accurate is that 350%? So, if money is no object, and you want to know exactly what dose you're getting, consider avoiding grapefruit altogether.

Edited by Jaris, 28 December 2016 - 07:28 PM.

[Kenbar]

I'll have to do more reading about Metformin. I have a prescription, but haven't started taking it yet.

The self-experimenting MD I'm in contact with takes 500mg every day. Which sounds like a lot compared to the 6mg of Sirolimus per week thhat he takes, but they work differently.

Rapamycin  can function as a metabolic “signaler” that inhibits a biological pathway. As I understand it, signaling doesn't use up the molecules, so it takes very little.

 

Just need to correct something I posted earlier: cancer patients sometimes take up to 90mg of Rapamycin (or similar drugs such as Everolimus) per WEEK (not per day as i said earlier).

 

The grapefruit trick was studied in order to help cancer patients who are taking large doses of several other potent drugs as well, causing digestion distress. Taking less by just drinking juice is a good thing. I'm a little concerned about extrapolating to much smaller doses: how accurate is that 350%? So, if money is no object, and you want to know exactly what dose you're getting, consider avoiding grapefruit altogether.

 

Well I must admit all this has got my interest level way up...but if I can't order it from Canada without a prescription I'm probably going to have to sit on the sidelines for now. I might try ordering it middle of next month N see if that works...I'm assuming it won't, but nothing lost for trying.

Edited by Kenbar, 28 December 2016 - 10:46 PM.

[tintinet]

500 mg is a fairly low dose for metforomin.

[maxwatt]

500 mg is a fairly low dose for metforomin.

 

500 mg is standard tablet.  Starting dose for most type II diabetics is 500 mg twice a day.

[Valijon]

Iirc, max daily dose of metformin for diabetics is 1700mg per day. Grapefruit potentiates many medications so this shouldn't be a surprise regarding the Rapamycin.

I'm very interested in the results of the human trials.

[FrankT.Hippo]

 

 

 

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.

 

 

 

 

The list is quite similar to what I have been taking for my mito disease, which seems to have stabilized somewhat. I talked to my geneticist a couple of years ago about rapamycin (with the goal of upregulating mitophagy) and she thought the theory sounded fine, and that it would be worth trying, but she wouldn't prescribe it.

 

As I couldn't find a way to order it -- I tried ordering through sigma aldrich and shipping it to my apartment, but apparently they check  -- I stopped looking and tried other supplements, which seemed to work well for a while e.g., PQQ and MitoQ. 

 

I haven't come across research since that would less incline me to try rapamycin. The trick seems to be acquiring it without having to procure it through an untested Chinese retailer on Alibaba. 

 

 

What did you end up trying? If it was from India/China would you be interested in splitting the price to get it tested. (I would give you half the money to test your batch at e.g.,  http://www.ecstasydata.org/about.php + for heavy metals). And then I would order my own batch -- if I can't find anyone to split it with -- and get that tested. I probably spend about 10k a year on "mitococktail" supplements and given my constant experimentation -- and delicate health -- it would be well worth the money knowing that I was taking the actual stuff.      

[Jaris]

First I tried a lab in China, which seems to have just taken my money and is now ignoring me. Not a big surprise.

i'm working on something else but I'm not sure how it will go. PM me and I'll fill you in.

Edited by Jaris, 05 January 2017 - 06:15 AM.

[Valijon]

What about ordering from international drug mart .com? They are out of India. They have Rapamycin.

[Jaris]

What about ordering from international drug mart .com? They are out of India. They have Rapamycin.

 

If anyone tries this approach, please let everyone here know how it went. I've looked at similar sites (and now this one) and they all require a prescription. This one's a little sneakier in that it doesn't seem to have a FAQ where you can find this out. Instead, you have to accept their terms of service, and I didn't see a link to that until I had filled out my (fictitious) personal info. To save others the trouble, I've attached a txt document with those terms.

 

My second concern is that they are very expensive. $300 for 40 Sirolimus 1mg pills!

Attached Files

•  terms.txt   6.83KB   16 downloads