955 replies to this topic

[PAMPAGUY]

You will have to get a scientific scale that measures to .1 mg at least.  It would be worth the cost of the scale in the long run.  Make sure that it is calibrated correctly.  Will pass this to Dr. Green today, and see what he has to say.

 

Good Luck,

 

PAMPAGUY 

[Alpharius]

You can dissolve Rapamycin in 99% Ethanol, so something like 10 mg /  1 ml and use insulin syringes (100 IU), to properly dose. You would of course make a bigger stock solution maybe with 100 mg, so you can rely on your scale.

[DareDevil]

Hi Pampaguy,

 

I look forward to hearing Dr Green's recommendation (sent you a PM with personal details). I think this protocol will be interesting to explore, especially as I will already be adding retinoic acid and statins to the Rapamycin and Metformin.

 

 

Hi Alpharius,

 

Thanks for your dilution suggestions. I will dilute it into liquid starting with 100mg / 10ml as this should last me several months at 6mg/week. Would you also recommend I dilute the Metformin? If so, what solvent would it be best diluted into?? It would make its daily intake easier than tiny doses of volatile powder. I was able to do that with Dasatinib because it was occasional intake, but for something taken continuously year round at 500mg/day, it's important for its administration to be easy.

 

Cheers,

 

DareDevil

 

[PAMPAGUY]

I'm not a big fan of diluting the powders?  Too many steps and chances for things to wrong.  Metformin is not a problem, but rapa could be.  You want to know the dosage that your taking for safety issues.  I looked at scales on Amazon and Ebay and it looks like you could get a good one for about $25-35.  It would only have an accuracy of 1 mg, but to get down to .1 mg cost a lot more, like $500.  If you were within a mg on the metformin you could care less, but on the rapa it could still work.  If you are taking 6 mg rapa, and you get 5 or 7 because of the limited accuracy of scale that would not be a big thing.  One question, did you guys know you were getting powder, or did you not ask?  If TLR is going to sell tablets, they would have to buy from India in order to be competitive.  Probably too many distributors involved.

 

Will update later today on my meeting with Dr. Green.

[DareDevil]

Hi Pampaguy,

 

I assumed it would be powder because this is what TLR has shipped me before for other substance purchases. They're a bulk supplier even if in this case due to high production costs the bulk quantities are tiny little envelopes. This keeps the prices at their lowest possible making for bang for the buck experimentation.

 

My electronic scale mesures from 0.001g to 20g so 500mg will be easy enough to weigh out and keep in powder form, dropping it for intake into a yoghourt, for example. The Rapamycin's very small dosage might be harder to get right but its feasible plus 6mg is a ballpark number and doesn't need to be exact and can be a gram more or a gram less. I am thinking of simply adding it to 100 proof rum, and keeping it in a small glass vial in the fridge. Or I could dilute it in Grapefruit juice?  Just kidding of course, that would be scary stupid unless I was ready to dose very very low.

 

For the other substances and their dosage, thanks for sharing what Dr Green thinks about that.

 

Thanks for your advice.

 

DareDevil

[malbecman]

 Yes, weighing out 6mgs accurately is pretty difficult but if you can live with +/- 1mg, you should be fine and having to only do it 1x/week helps.   If you had to do it daily, it would get old pretty fast.
 
Liquid dosing can be more handy as you are weighing out more to begin with (say, 100mgs) which is easier to do and making a known concentration (say 10mg/ml using 10mls rum).  Then you just get your syringe out every time and take 600ul (0.6ml) and down the hatch.
 
 I'm considering getting some from TLR and starting my dog on it as well (and then likely me).

Addendum: I looked up the solubility. While its decent in ETOH (50 mg/ml), its really poor in H20 and so rum, unless it was 150-190 proof kind, might not work so well. You'd probably end up with a suspension which could still work....you'd just need to shake it and disperse well before every time you took a sample.

Edited by malbecman, 12 May 2017 - 06:07 PM.

[DareDevil]

Hi Malbecman,

 

Thanks for the advice about it's ability to dissolve and be in a constant concentration throughout the solution. I guess I'd need to shake it well and take my sample fast before it settles. I appreciate the heads up!

 

Cheers,

DareDevil

[PAMPAGUY]

Hi DareDevil,

 

Well I had my appt. with Dr. Green and the following is what I learned.  Number one is that most everything that you need to know is on his website if you will spend the time to read it over and over until you grasp everything.  He breaks down all the drugs used in the ageing formula and cites cases.

 

Dr. Green is taking 1000 mg Metformin now instead of 500.  Helps to control blood sugar and food cravings as well as inhibiting TORC 1.

He is also open to increasing the amount of rapa within certain limitations.  First rule is to stay on the once weekly dose to allow the drug to reach the (trough level in stead-) before the next dose.  If one is taking 6 mg once a week, you could increase it to 7,8 or 9 for a few weeks to see if you have any side effects.  The most common side effect is mouth ulcers (sores).  Many others are listed in the elderly trial on immune function quoted here may times.  (mTOR inhibition improves immune function in the elderly 2014).  Once you start to get a side effect like ulcers, a bad cold, etc. back off 1-2 mg in your dosage because your immune system is telling you that it's being compromised instead of being helped.  I took my increased dose of rapa today. (went from 6 mg to 9 mg)   Will stay on the dose for the foreseeable future.  Very close observation of any side effects.  If I get any, will back off to 7 mg.  I believe their is a sweet spot on dosage, but it is different for different people.  In the elderly trial, the 5 mg once weekly did as good as the 20 mg once weekly.  In the mouse studies the younger mice achieved no additional benefit of taking rapa at a young age versus starting it at 600 days. (60-65 yo)

It seems to say, wait until your 60 before using it.

 

One of the elements of the ageing formula is age induced obesity.  Calorie Restriction - -This is cured by taking up to 2000 mg Metformin daily.  The Metformin helps curb you appetite.  It is not a weight reduction drug per se, but it helps you lose weight.  Rapa also helps because it pulls the fat out of your cells to be turned into waste.  I personally have been taking 2000 mg daily for 2 months have lost 10 lbs, and even more fat.  I can honestly say it is easier to say no to food, and to get fuller faster.  It keeps your insulin level lower and that is good.  No side effects so far except my stools are darker.  I think that is the fat that I'm losing.

 

Taking the Candesartan is important and he recommends 16 mg daily for someone without blood pressure problems.  This is not that cheap.  I was quoted $75 for 90 tabs of 16 mg at Costco. (.83 tab)  Others are more money.  I have high blood pressure, so I'm taking 16 mg twice a day.  I'm checking with my source now for pricing for 500 tabs.  Might also be cheaper to buy 32 mg and split it.

 

I paid $125 for 550 1000 mg Metformin SR from India.  My source will drop ship different drugs to different addresses if one person pays for it all.  Of course any individual person can order, it is just more expensive because you don't get volume discounts and you have to pay by bank wire.  One person pays and get a big discount for volume and then they drop ship to different people and addresses.  I haven't tried that, but this is what they do all over the world for businesses.  In fact the company is dropshipmd.com.  I believe there on facebook also. They do not take PayPal, or credit cards when you don't have Rx.  Bank wire only.  I have ordered rapa and metformin from them.  They are very good, in that they pay for shipping, but it takes 4-5 weeks for shipment.  My bank charges $25 for a wire of any amount of money.

 

Back to Dr. Green.  He is a elderly man who's mind and thin body is very sharp.  He doesn't live in a very nice house and his van has seen better days.  I don't know what he did will all his money, but that was too personal to ask.  He was very nice, and examined me and took 2 1/2 hours total time just talking about the formula and delaying ageing.  He gave me some very generous rx's for rapa (600 mg), metformin (1000 x 1000 mg tabs), and Candesartan (16mg x 400).  All drugs are for off label use.  These were very official scripts with the New York numbers, bar codes and everything.  All of his diplomas were posted above his desk.  If you don't have part B medicare for Rx's or some other Rx plan they can be very expensive to fill.  So for many people, India or TLR is the solution.  I will be waiting for the feedback from everyone using the powders to see how that goes.  It cost me $100 roundtrip to fly from Boston to NY, Uber to his office, and $350 for his fee.  I could afford it and it was well worth it to me.  I learned a lot.  He also said to monitor you Fasting Insulin level when you get your routine blood test which should be every 3 months when you messing with rapa.  Insulin level is check in your blood and it should be around 4-6.  Google it to see the normal range.

 

I want to caution everyone about the experimental nature of what some of us are doing.  We do not know the long term effects of taking rapa weekly for ever.  Dr. Green takes 6 mg weekly for 17 months without noticeable side effects, but no one knows what the future holds.  We may find out that taking rapa for 3 months then 24 months off is just as good or better.  We don't know at this point.  He takes 6 mg weekly because it almost completely (99%) washes out of his system before the next dose.  No residual build up into the next dose.

 

Honest feedback is welcome

 

 

Edited by PAMPAGUY, 13 May 2017 - 12:31 AM.

[Valijon]

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

[tintinet]

Group rapamycin buy (tablets)?

[Jaris]

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

 

Personally, I think 40 or 45 would be a good age to start with this. Maybe at lower doses and/or longer periods. Maybe 2mg/week, or 4mg/2 weeks. I have little to go on, but it seems like 40 -45 could well be considered to be mid-life. Our distant ancestors rarely lived to 65.

 

Edited by Jaris, 13 May 2017 - 03:22 AM.

[Valijon]

I would think we would all want to start taking anything we could to extend lifespan and healthspan as soon as we had finished becoming adults. I was at a loss to figure out why rapamycin wouldn't work for those of us who had reached middle age.

[Jaris]

Group rapamycin buy (tablets)?

 

I have enough for 10 more months, but if the price is right, and if we can verify the mfg is legit, I would be interested.

[PAMPAGUY]

Jaris and Valijom,

 

Taking rapa formula before 60 yo.   Just remember what rapa does.  By inhibiting the signal to TORC 1, it is getting rid of bad senescent cells.

https://www.fightagi...enescent-cells/

 

In other words at ages under appx. 60 years you do not have the problem of bad senescent cells which makes you age and all the diseases that go with that.  Your immune system is strong.  In mouse studies they gave young and old mice rapa until death.  They all lived longer, but there was little or no benefit to taking rapa at a earlier age.  A normal person in his 50's can run marathon's and really improve his body and stamina, but once ageing kicks in that is not possible.  Then you want a delaying action by using the rapa formula.  To delay death and ageing and by doing that you are delaying all the diseases that go with it.  If you really want to learn, read Dr. Greens website and all the cites listed there and all your questions will be answered.

 

Rapa is not a fountain of youth.  A young person is not going to get more energy, and get younger.  The best an ageing person can do it delay death for as long as possible until something better comes along, and I believe that will happen in the next 10-20 yrs.

 

If I was under 60, I would not even think of experimenting with rapa, but would concentrate on healthy eating and exercise in order to feel good and strong.  The age of 60 is considered middle age for mice and people when it comes to ageing.  Somewhat different than normal thinking, but if a person is going to live to 90 or above it makes sense.

 

One person's opinion.

Edited by PAMPAGUY, 13 May 2017 - 11:45 PM.

[MikeDC]

Good points. Plus all the side effects will be much more than any benefits Rapa gives a younger person.

If you are in the 30's just exercise and eat healthy. If you are in the 40's and 50's, take Niagen. Wait for more clarity on Rapa. Personally I believe Niagen has all the benefits of Rapa without the side effects.

[Alpharius]

I disagree with the opinion that aging is something that happens late in life and that rapamycin only then after an age of 50 or 60 years has an effect on aging. I think aging or what we mostly experience as aging starts from the point when we have fully grown into adults, but the programms which lead to that development run further (Blagosklonny). 

 

Rapamycin slows down aging in middle age, but the effect is probably more pronounced in the late age because Rapamycin has an antineoplastic effect. Rapamycin decreases mid-life mortality, when it is given mice earlier, starting from 270 days of life, so yes it has also an important effect on your survival if you are younger. http://www.nature.co...ature08221.html
 

[Skyguy2005]

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

 

Personally, I think 40 or 45 would be a good age to start with this. Maybe at lower doses and/or longer periods. Maybe 2mg/week, or 4mg/2 weeks. I have little to go on, but it seems like 40 -45 could well be considered to be mid-life. Our distant ancestors rarely lived to 65.

 

I remember reading about a Chinese guy in Han Dynasty who lived to 109. Obviously this isnt "official".
 

Edited by Skyguy2005, 14 May 2017 - 01:41 PM.

[tintinet]

https://www.mdlinx.c...month&page_id=1

New function discovered for compound that may help slow aging
Oregon State University News

Edited by tintinet, 14 May 2017 - 02:09 PM.

[maxwatt]

The caution on not starting rapamycin in early middle age may be that, except anecdotally,  no one has studied its effects except in aged mice, so far.  Aging kicks into high gear in one's sixties.  You 40-year olds ain't seen nothing yet.  It may be beneficial even in one's thirties, maybe damaging.  Age forty is where the decline in a man's strength and endurance noticeably decline despite exercise.  Women not until after menopause.

 

On mixing powders:  I would not use a liquid, at least for long term storage.  Possible instability, decomposition.  One might mix a white powder like rapamycin with a colored one, like tumeric, to be able to judge when the mixture is complete and uniform.  A ratio of 10:1 would enable then allow dosing more accurately, 30 mg rather than 3mg.  I am not comfortable with this, as it is still difficult to do this properly in one's kitchen.  Any pharmacists have suggestions?

 

Dosing is especially critical with rapamycin, as the difference between an effective dose and one that causes mouth sores or worse side effects is slight. If self-experimenting, I would pay more for tablets from a pharmaceutical company.  They are good at measuring consistent accurate doses.

[Skyguy2005]

What does rapamycin feel like to take anybody? I say this as someone who feels something with lots of supplements (even just stuff like garlic).

[Michael]

The caution on not starting rapamycin in early middle age may be that, except anecdotally,  no one has studied its effects except in aged mice, so far.

 

Actually, there are now lots of studies across a wide range of ages of initiation. It's certainly true that lots  of work has been done in old and early-old mice, which is really the most important group to study: this includes he original, breakthrough study, which started at 19 months, entirely by accident as a result of a faulty rapa formulation, and the same age of initiation was used in PMID 23682161, and similarly the study that triggered this thread  (PMID 27549339) started the animals at 20–21 months of age. There are also short-term studies on cardiac and immune function that started as late as 24 mo.

 

However, there are successful LS studies with mice started on rapa at 9 mo (PMID 20974732), 2 mo (PMID 22107964 (though this wasn't a good test, due to short-lived controls)), and PMID 23863708 actually used 3 different cohorts that started at 4, 13, and 20–22 mo.

 

Figure from the Harrison lab at The Jackson Laboratory.

 

Although it's preliminary, the average  age at the start of treatment in the recent pilot for the rapa dog study was 9.7 ± 1.84 y, and so included 4 dogs aged 6.6-7.2. 

Edited by Michael, 15 May 2017 - 04:43 PM.

[VP.]

What does rapamycin feel like to take anybody? I say this as someone who feels something with lots of supplements (even just stuff like garlic).

 

Feels like nothing. The only effect I can say for sure is Rapamycin are mouth sores. I had that two times with my early dosing and never again even though my protocol has not changed. I do every two weeks at 2-3 mg with grapefruit juice. Have not been sick since starting and I feel fine. In my late 50's. 

[to age or not to age]

My wife and I have been taking rapamycin for 4 months - 3 and 4 mg respectively once a week. I had a few short lived mouth sores early on and

a small sty on one eye and then the other. There have been no new side effects over the past 2 months. My wife said, "I don't feel any different" and this includes  the fact  we also take NR (BASIS), resveratrol and curcumin daily. My response to her was, I don't think humans are built to be acutely aware of

changes in how they feel, when the changes occur slowly. The body seeks equilibrium on a "How I feel level" for the sake of sanity, I think. So subjective

how you do feel measurements probably say little.  However, as a third party, observing my wife, she seems a bit more fit, is running more, able to

concentrate for longer periods as an attorney.  Her skin is excellent. 

[maxwatt]

 

The caution on not starting rapamycin in early middle age may be that, except anecdotally,  no one has studied its effects except in aged mice, so far.

 

Actually, there are now lots of studies across a wide range of ages of initiation. It's certainly true that lots  of work has been done in old and early-old mice, which is really the most important group to study: this includes he original, breakthrough study, which started at 19 months, entirely by accident as a result of a faulty rapa formulation, and the same age of initiation was used in PMID 23682161, and similarly the study that triggered this thread  (PMID 27549339) started the animals at 20–21 months of age. There are also short-term studies on cardiac and immune function that started as late as 24 mo.

 

However, there are successful LS studies with mice started on rapa at 9 mo (PMID 20974732), 2 mo (PMID 22107964 (though this wasn't a good test, due to short-lived controls)), and PMID 23863708 actually used 3 different cohorts that started at 4, 13, and 20–22 mo.

...

Thanks for the references.  My mistaken assertion might have been accurate a few years ago.  Here's another recent study: PMID 23648089. which found, among other things, that "Dietary rapamycin increased HBA1c over the first 3 weeks of treatment in young animals, but the effect was lost by 3 months, and no effect was detected in older animals."

Rapamycin was found to increase glucose intolerance, but insulin resistance was not increased as shown by a normal response to a glucose tolerance test.  I would say this needs to be repeated in human subjects before making conclusions.

[maxwatt]

 

What does rapamycin feel like to take anybody? I say this as someone who feels something with lots of supplements (even just stuff like garlic).

 

Feels like nothing. The only effect I can say for sure is Rapamycin are mouth sores. I had that two times with my early dosing and never again even though my protocol has not changed. I do every two weeks at 2-3 mg with grapefruit juice. Have not been sick since starting and I feel fine. In my late 50's. 

 

 

I am a relatively aged rat.  5 mg once a week.  No significant change in glucose levels or A1c. A feeling of well-being, almost euphoria for two or three days after dosing.  Non-osteo arthritic symptoms in fingers greatly diminished, returning toward the end of a week, but not as severe as prior.   Each dose reduces symptoms overall. Range of motion regained, but residual pain and stiffness still remain,  Hoping improvement continues.  This may be an antibiotic effect rather than anti-aging per se, but I'll take it.

[tintinet]

What does rapamycin feel like to take anybody? I say this as someone who feels something with lots of supplements (even just stuff like garlic).

Certainly nothing consistent. At 3 mg thought I felt mild euphoria, but not so at 4 and 5 mg. Likely just placebo effect or just circumstantial.

[malbecman]

 I ordered some from TLR and will check it out via high-res mass spec.  (I'm guessing its good to go...the price is pretty comparable to what I can get from chemical supply houses).  I must say, they were very responsive and had great customer service.   My dog is ~14.5 and pretty aged so we'll see how she does.

[Skyguy2005]

 

What does rapamycin feel like to take anybody? I say this as someone who feels something with lots of supplements (even just stuff like garlic).

Certainly nothing consistent. At 3 mg thought I felt mild euphoria, but not so at 4 and 5 mg. Likely just placebo effect or just circumstantial.

 

 

OK. I get a strong feeling from certain supplements (I'm 28), especially herbs. Most famous herbs e.g. garlic turmeric fenugreek or even hops in IPA beer or chemicals in red wine give me a little buzz. Like an uplifting feeling. A physical sensation nothing to do with psychology or emotion. Probably strongest is Red Reishi mushroom, also Ginkgo and amongst minerals selenium. Bizarrely, if I took a multimineral, or zinc or copper beforehand, the feeling was "blocked". Selenium seems to strengthen it, as does NAC but not vitamins A C or E. The minerals thing made me think it might be chelation, but I tried IP6 and felt only a slight buzz, very faint.

 

I would be so fascinated to try rapamycin. My best hypothesis given that mushrooms seem to be very strong (especially Reishi) is that it is an immune thing, and I know rapamycin is immunomodulatory. When I take some things like Reishi I have noticed a slightly running nose, like the immune system said "hey", without any illness but instead feeling uplifted. This fits NAC too because NAC can strengthen the immune system.

 

OTOH, the only mushroom I haven't got a big feeling from was cordyceps, which has some immunosuppressive things like rapamycin. So maybe I wouldn't feel anything.

[Jaris]

My wife and I have been taking rapamycin for 4 months - 3 and 4 mg respectively once a week. I had a few short lived mouth sores early on and

a small sty on one eye and then the other. There have been no new side effects over the past 2 months. My wife said, "I don't feel any different" and this includes  the fact  we also take NR (BASIS), resveratrol and curcumin daily. My response to her was, I don't think humans are built to be acutely aware of

changes in how they feel, when the changes occur slowly. The body seeks equilibrium on a "How I feel level" for the sake of sanity, I think. So subjective

how you do feel measurements probably say little.  However, as a third party, observing my wife, she seems a bit more fit, is running more, able to

concentrate for longer periods as an attorney.  Her skin is excellent. 

I hate to be a wet blanket, but curcumin has been shown to reduce the bioavailability of rapamycin (Everolimus, which is a rapamycin analog - or rapalog). The discussion of this is back about a page, so I'll copy it here:

 

Oral intake of curcumin markedly activated CYP 3A4: in vivo and ex-vivo studies

Curcumin, a specific secondary metabolite of Curcuma species, has potentials for a variety of beneficial health effects. It is nowadays used as a dietary supplement. Everolimus (EVL) is an immunosuppressant indicated for allograft rejection and cancer therapy, but with narrow therapeutic window. EVL is a substrate of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4). This study investigated the effect of coadministration of curcumin on the pharmacokinetics of EVL in rats and the underlying mechanisms. EVL (0.5 mg/kg) was orally administered without and with 50 and 100 mg/kg of curcumin, respectively, in rats. Blood samples were collected at specific time points and EVL concentrations in blood were determined by QMS® immunoassay. The underlying mechanisms were evaluated using cell model and recombinant CYP 3A4 isozyme. The results indicated that 50 and 100 mg/kg of curcumin significantly decreased the AUC0-540 of EVL by 70.6% and 71.5%, respectively, and both dosages reduced the Cmax of EVL by 76.7%. Mechanism studies revealed that CYP3A4 was markedly activated by curcumin metabolites, which apparently overrode the inhibition effects of curcumin on P-gp. In conclusion, oral intake of curcumin significantly decreased the bioavailability of EVL, a probe substrate of P-gp/CYP 3A4, mainly through marked activation on CYP 3A4.

[Jaris]

I'm pushing 60, and other than a moderate case of Parkinson's I'm in pretty good shape for my age. I'm back to jogging a mile, doing 40 pushups, etc. Jogging is actually easier for me than walking.

I've been taking rapamycin for almost 5 months. Started at 6 mg/week but because I'm taking it also for parkinson's, I upped it to 9 mg/week 2 months ago.

Apart from some minor mouth sores when i started, i've noticed no negative side effects. My glucose level is fine (I was not pre-diabetic before).

On the plus side: i have more stamina, lost about 10 pounds, and I generally feel better for few days after dosing. Sort of the feeling you get after a good work-out.