LONGECITY

Interested in seeing how people are using rapamycin and what they've experienced so far. Please answer the survey!

 

 

As a ballpark figure, I worked out that 1 in 5 patients taking rapamycin for 5 years might be expected to develop diabetes, if we go by this study.

 

The study found that over roughly a 4.5 year period, in patients taking rapamycin with cyclosporine A, the diabetes incidence was 31.6%, whereas in kidney transplant patients taking cyclosporine A alone, the diabetes incidence was 10.4%.

More recent studies indicate that many of the negative effects of rapamycin are mitigated or eliminated by intermittent dosing, with at least 5 days and probably 7-10 days between each dose.

So it may not be possible to draw any conclusions from data regarding people who took it every day.

See: https://www.ncbi.nlm...pubmed/26463117

As a ballpark figure, I worked out that 1 in 5 patients taking rapamycin for 5 years might be expected to develop diabetes, if we go by this study.
 
The study found that over roughly a 4.5 year period, in patients taking rapamycin with cyclosporine A, the diabetes incidence was 31.6%, whereas in kidney transplant patients taking cyclosporine A alone, the diabetes incidence was 10.4%.
 
So as a crude calculation, we might subtract one percentage from the other in order to estimate what the incidence of diabetes would be in patients taking just rapamycin, and this works out at around 21%, or around 1 in 5.
 
The study does not indicate the dose used, but here it says the rapamycin maintenance dose for kidney transplant patients is 2 mg to 5 mg per day.

 

Yes, intermittent dosing, and also taking metformin along with rapamycin, may reduce or eliminate the risk of developing diabetes, though only theoretically (ie, this has not been proven in any studies). 

What also hasn't been proven in any studies is that intermittent dosing of rapamycin does cause diabetes. You seem to have an agenda here.

Your initial claim that 20% of rapamycin users are likely to contract diabetes within 5 years doesn't take into account that these patients were ALSO taking cyclosprine A, which itself is associated with NODAT or New Onset Diabetes.

See this meta-analysis study:
http://journals.plos...al.pone.0160421

NODAT rate at 12 months after transplantation was reported in five of the studies, with 101 of 748 patients on ciclosporin compared with 168 of 733 on tacrolimus experiencing NODAT after transplantation

So ciclosporin (which is the same as cyclosporine: https://en.wikipedia...i/Ciclosporin),caused diabetes all by itself. When taken with another agent which can also induce diabetes, the effect is likely to have been much stronger.

You also didn't take into account the evidence that intermittent dosing doesn't affect beta cells, according to the study I cited.

So yes, maybe taking rapamycin every 5-10 days could cause diabetes, but we don't have enough evidence to say one way or the other at this point, and there is some evidence that it's not likely to.

 

More recent studies indicate that many of the negative effects of rapamycin are mitigated or eliminated by intermittent dosing, with at least 5 days and probably 7-10 days between each dose.

 
Yes, intermittent dosing, and also taking metformin along with rapamycin, may reduce or eliminate the risk of developing diabetes, though only theoretically (ie, this has not been proven in any studies).

What also hasn't been proven in any studies is that intermittent dosing of rapamycin does cause diabetes. You seem to have an agenda here.

 

I am just pointing out the possible serious side effects of a drug, in order that people can be better informed.

 

I am currently taking rapamycin myself in a short term trial to see whether it improves my ME/CFS (several people found this drug made significant improvements for their chronic fatigue syndrome — see this thread). That's why I've tried to assess the possible risks, and looked at how one might mitigate them. I summarized my findings in this post, which also explains the likely mechanism by which rapamycin may increase diabetes risk.

 

By the way, if you want to save money, taking CYP3A4 inhibitors such as ketoconazole or grape fruit juice increases blood levels of rapamycin by 350% to 500%, which means you can lower your dose by 3.5 to 5 times. For more info, see this post. 

 

 

 

So we seem to be entering an area of uncertainty about just how likely it is that rapamycin will trigger diabetes. In my case, I have a serious illness of ME/CFS that keeps me housebound and unable to work; so if rapamycin were able to make major improvements in my ME/CFS, I would take it anyway, even with the uncertainty about diabetes.

 

But for healthy people taking rapamycin just for general health improvements or longevity purposes, those people may want to consider this diabetes question mark.

Edited by Hip, 28 October 2017 - 08:01 PM.

I won't have any lab results for another 2 months to compare before and after results. The most noticeable and I firmly believe real effect of rapamycin is weight loss. I lost about 6-7% of my weight in about 4 months, I am hearing from other rapamycin users that weight loss is happening, is sustained, and is effortless with no major changes in diet. Excess weight is a strong predictor of mortality so that's welcome.  If you can put weight loss percent in the survey that would be informative. I have heard from a couple rapamycin users that blood glucose has gone down after supplementation. Dose is the poison. You want to inhibit mTORc1 without inhibiting mTORc2. 

 

https://twitter.com/...933918306680832

 

 

Edited by VP., 29 October 2017 - 05:35 PM.

Weight gain or loss would be a great one to add. Unfortunately I'm not seeing any way for me to edit the poll now.

I won't have any lab results for another 2 months to compare before and after results. The most noticeable and I firmly believe real effect of rapamycin is weight loss. I lost about 6-7% of my weight in about 4 months, I am hearing from other rapamycin users that weight loss is happening, is sustained, and is effortless with no major changes in diet. Excess weight is a strong predictor of mortality so that's welcome.  If you can put weight loss percent in the survey that would be informative. I have heard from a couple rapamycin users that blood glucose has gone down after supplementation. Dose is the poison. You want to inhibit mTORc1 without inhibiting mTORc2. 
 
https://twitter.com/...933918306680832

Having just started an experiment yesterday it would be best to wait before responding to the poll.

 

However, within two hours of taking the very first 5-6 mg dose of Rapamycin there was a sudden onset of a sore mouth/throat. It was mild to moderate in severity and has almost resolved a day later with no detectable mouth sores.

 

Has anyone experienced anything like that? Any thoughts on what it might mean?

I do wish people would get blood work done before and after using any promising protocol.  Too many for the respondents to this poll seem not to be doing blood work at all. 

This section represents what I believe to be just about the total extent of knowledge regarding side-effects from long-term use of weekly rapamycin. The reason for the potential enormous difference between daily side-effects and weekly side-effects is directly related to the half-life of rapamycin. The FDA section on rapamycin says elimination half life is 62+/- 16 hours. Daily dose is every .4 half-lives and weekly is every 2.7 half-lives.Taking a drug once every 0.4 half lives or once every 2.7 half lives can have a profound impact on effects and side-effects. In the paper, "mTOR inhibition improves immune function in the elderly, Joan Mannick, December 2014, writes "adverse events are related to pre-dose (trough) concentrations". Trough concentrations are high after .4 half lives and low after 2.7 half-lives. Transplant medicine needs to prevent low trough concentrations to prevent acute rejection; but anti-aging medicine wants low trough concentrations to prevent side-effects.  

SIDE-EFFECTS RAPAMYCIN WEEKLY 6 MG FOR 14 MONTHS:     

                                                                15-Nov    16-Aug    16-Dec    17-Mar 
Glucose                                                        89             73           84            86 
HgA1c                                                             -                6            6.2          5.9 
Insulin with fasting glucose                        -                -               -             6.3 
Creatinine                                               1.20H           0.9          0.92        0.94 
Cholesterol                                                114           102           140         173 
HDL                                                               54             54             52            56 
LDL                                                                42             37             78         103 
TG                                                                 89              55             49            68 
Hemoglobin                                                13L            12.1L       12.5L     12.3L 
Hematocrit                                                 39.5            37.4L       37.7L     36.2L 
WBC                                                              6.1             6.3           2.6L         4.9 
Lymphocytes                                            1129            901          660L        706L    

1/1/16: 172 pounds;  3/22/17: 150 pounds.

 Waist/hip ratio start: 38/38 inches; waist/hip ratio 1 year: 33/36 inches.

 Lipitor 80 mg start 10/15 for angina; Stop Lipitor 9/16 causing Gout.

 Analysis: Glucose metabolism: rapamycin caused mild glucose intolerance. Insulin level 3/17 was normal and showed insulin sensitivity. Combination of glucose intolerance and insulin sensitivity is benign and not pre-diabetic. 

Renal: Decrease in creatinine from elevated to normal was extraordinary.

 Lipids: Dramatic results from Lipitor regarding LDL with low of 37 and increase to 103 with stopping lipitor. No apparent effect from rapamycin.

 Blood: Rapamycin increased mild anemia of 13 gm Hemoglobin before to 12.3 gm. Indices normal. Mild anemia is real side-effect. Decrease in absolute lymphocytes.

 Overall: glucose intolerance, insulin sensitivity, improved renal function, mild anemia, decrease lymphocytes.

 Clinical: No mouth sores in 14 months, (apthous stomatitis). No untoward clinical side-effects. 

Subjective impression: Miraculous improvement in health; feeling old to feeling young. 

This is a case report of ONE person, me, taking weekly rapamycin; for 14 months. Until a larger study is reported, I think this is the best source of information regarding expected side-effects from weekly rapamycin. Since rapamycin is clearly the most robust anti-aging drug ever discovered, it does seem a bit odd, that there would be data on only a single person; but it is, what it is.  

https://www.rapamycintherapy.com/

 

I find it odd that there would be a side effect within two hours of the very first  6 mg dose. 48 hours + later there is still a slightly raw tongue and throat but no actual mouth sores yet. I would expect this side effect to appear after a period of usage not right away. The plan was to take 6 mg every 7 days but a modification may be needed. 

 

Hip, according to Dr. Green (https://www.rapamycintherapy.com/) , drinking grapefruit juice while taking rapamycin is a BAD idea. 

I find it odd that there would be a side effect within two hours of the very first  6 mg dose. 48 hours + later there is still a slightly raw tongue and throat but no actual mouth sores yet. I would expect this side effect to appear after a period of usage not right away. The plan was to take 6 mg every 7 days but a modification may be needed. 

 

Hip, according to Dr. Green (https://www.rapamycintherapy.com/) , drinking grapefruit juice while taking rapamycin is a BAD idea

Form my experience and others I've heard from I would be surprised if those symptoms had anything to do with low doses of Rapa. There is a rapamycin facebook group for users that are taking Rapa for approved uses and it is a useful site to see side effects of large doses of rapa. The site does show you can take very large doses for years and live but unfortunately with unwanted side effects. 

 

Is taking rapa with grapefruit juice risky? Yes, but I believe as long as you are not getting mouth sores then 1mg of rapa with some juice is a way to lower the cost of supplementation. The problem is you never quite know how much you are getting. If you want to risk it to save money cut back  the juice if you get any sores and don't do more then once a week IMHO. 

Anecdotal report:

 

I have now taken two doses of rapamycin:

- 2mg on 18-Oct-2017

- 4mg on 27-Oct-2017

 

I also did a 5 day Fasting Mimicking Diet (my 4th) from 23-Oct-2017 through 27-Oct-2017.

 

I go to the gym 1-2 times a week and always do 30 minutes of cardio, always using the exact same machine with the exact same setting (interval training), always measuring my heart rate and making sure it goes below 129 before each "hill" and doesn't go above 150 nearly ever. My number of calories burned in that 30 minutes, as indicated by the machine have been, until starting rapamycin, about 220 + or - 10 calories.

 

On October 30 I did the same routine, and found that my heart rate stayed lower than usual, so I increased my intensity to keep it roughly at the same BPM. Calories burned was 279.

 

Today (November 3) I did the same routine again and found that I had to work even harder to get my heart rate up, and also found that it fell back down to lower BPM much quicker than before. Total calories burned 289, but I didn't manage to get my heart rate up to where it normally has been.

 

As usual, there are confounding factors: the fasting mimicking diet, NR supplementation, etc. But I've been doing those for several months, and haven't noticed a change like this until now.

 

Where did you all sourced your rapamycin from?
I finally was able to obtain metformin but I couldn’t find myself rapamycin.

Anecdotal report:

I have now taken two doses of rapamycin:
- 2mg on 18-Oct-2017
- 4mg on 27-Oct-2017

I also did a 5 day Fasting Mimicking Diet (my 4th) from 23-Oct-2017 through 27-Oct-2017.

I go to the gym 1-2 times a week and always do 30 minutes of cardio, always using the exact same machine with the exact same setting (interval training), always measuring my heart rate and making sure it goes below 129 before each "hill" and doesn't go above 150 nearly ever. My number of calories burned in that 30 minutes, as indicated by the machine have been, until starting rapamycin, about 220 + or - 10 calories.

On October 30 I did the same routine, and found that my heart rate stayed lower than usual, so I increased my intensity to keep it roughly at the same BPM. Calories burned was 279.

Today (November 3) I did the same routine again and found that I had to work even harder to get my heart rate up, and also found that it fell back down to lower BPM much quicker than before. Total calories burned 289, but I didn't manage to get my heart rate up to where it normally has been.

As usual, there are confounding factors: the fasting mimicking diet, NR supplementation, etc. But I've been doing those for several months, and haven't noticed a change like this until now.

Hi,

Can you link me (or detail about) your 5 day Fasting Mimicking Diet? Sounds interesting.

There is info/research on fasting mimicking diet (FMD) at prolon which is one of the two companies that sells a ready to eat 5 day diet:

 

https://prolonfmd.co...mimicking-diet/

 

the other company is https://www.lifebox.diet/

 

I did the lifebox 5 day diet awhile back and it was very easy. 

 

You can also just google fasting mimicking diet and find recipes and roll your own.
 

 

The lifebox includes gynostemma i.e. Jiaogulan tea which is worth taking (unless you are taking metformin or berberine).

 

 

 

 

 

 

dropshipmd

 

Where did you all sourced your rapamycin from?
I finally was able to obtain metformin but I couldn’t find myself rapamycin.

 

Edited by smithx, 04 November 2017 - 03:20 AM.

A source of powdered rapamycin can be found at  https://teamtlr.com

 

For 1 mg tablets from India you can try https://dropshipmd.com

 

https://www.cell.com...4131(15)00224-7

 

 

As usual, there are confounding factors: the fasting mimicking diet, NR supplementation, etc. But I've been doing those for several months, and haven't noticed a change like this until now.

Hi,

Can you link me (or detail about) your 5 day Fasting Mimicking Diet? Sounds interesting.

 

 

Edited by smithx, 04 November 2017 - 03:21 AM.

Those "Lifebox" boxes seem very expensive for what is provided.

As usual, there are confounding factors: the fasting mimicking diet, NR supplementation, etc. But I've been doing those for several months, and haven't noticed a change like this until now.

Have you thought about nixing the FMD and NR and seeing what happens with rapa and your lowered heart rate?

Also, since you're right start of dosing, maybe give yourself the gift of a basic, doctor-checkup blood panel?

dropshipmd

Where did you all sourced your rapamycin from?
I finally was able to obtain metformin but I couldn’t find myself rapamycin.

Thanks!
I’ll try to source some from there. It seems like I have to put in some sort of enquiry.

Those "Lifebox" boxes seem very expensive for what is provided.

 

True.  Mostly convenience though you do get a 30 min phone call with the guy who founded lifebox who knows more about FMD than most of us do and can make suggestions that may be very helpful for some people.  

Benko, that 30-minute phone call alone might be worth what they are charging. 

 

recon,  dropshipmd quoted me close to $600 for 320 1 mg tablets/capsules. It was $1.75 each plus shipping, which according to some members, has taken 4-5 weeks. Instead I obtained 500 mg (over 50% more quantity) for about $200 which is one-third the price. And I received the product within one week. Of course you must weigh out the powder but a $24 scale from Amazon ( https://www.amazon.c...0?ie=UTF8&psc=1 ) easily solved that issue.

If you are weighing 1-6mg, a $24 scale will not be accurate enough.

 

Since rapamycin doses are so small, it's really a good idea to get pre-measured amounts in pills, if you are going to take it.

 

Benko, that 30-minute phone call alone might be worth what they are charging. 

 

recon,  dropshipmd quoted me close to $600 for 320 1 mg tablets/capsules. It was $1.75 each plus shipping, which according to some members, has taken 4-5 weeks. Instead I obtained 500 mg (over 50% more quantity) for about $200 which is one-third the price. And I received the product within one week. Of course you must weigh out the powder but a $24 scale from Amazon ( https://www.amazon.c...0?ie=UTF8&psc=1 ) easily solved that issue.

 

Very true about the accuracy of that scale. We are using an aliquot method to dramatically reduce any variability.

 

Buying a drug from India certainly comes with some risk as well. Biocon appears to be a legitimate company and if dropshipmd really sends that brand maybe you are getting what you have ordered. But there have been problems with pharmaceutical companies from India (and other countries as well):

https://www.consumer...-safe/index.htm

 

For more peace of mind one might want to make an appointment with Dr. Green in New York who will then prescribe rapamycin that can be purchased from Canada.

Benko, that 30-minute phone call alone might be worth what they are charging.

recon, dropshipmd quoted me close to $600 for 320 1 mg tablets/capsules. It was $1.75 each plus shipping, which according to some members, has taken 4-5 weeks. Instead I obtained 500 mg (over 50% more quantity) for about $200 which is one-third the price. And I received the product within one week. Of course you must weigh out the powder but a $24 scale from Amazon ( https://www.amazon.c...0?ie=UTF8&psc=1 ) easily solved that issue.

$600 for 320 seems quite expensive.
At that price I can be filling myself with megadoses of NR.

I don’t really deal with bulk powders (unfortunately). Otherwise most of my supplements could’ve been bought a lot cheaper.

Rapamycin sells for at least $4 mg in US with RX. $1.75 is cheap. Rapa is serious medicine and has extended lifespan in every species tested. 5-6 hundred dollars a year is very cheap to save your life. Rapa is not an ordinary supplement. Probably shouldn't be used by anyone under 60. It is a poison if misused. See the following about anti-ageing formula. http://www.impactjou...33&path[]=57761

Rapamycin sells for at least $4 mg in US with RX. $1.75 is cheap. Rapa is serious medicine and has extended lifespan in every species tested. 5-6 hundred dollars a year is very cheap to save your life. Rapa is not an ordinary supplement. Probably shouldn't be used by anyone under 60. It is a poison if misused. See the following about anti-ageing formula. http://www.impactjou...33&path[]=57761

Points taken. I didn’t mean to appear rude. I was just shocked by the price.

I’ve contacted them and will be getting the quote soon. I will probably put in an order really soon.

At the meantime, I’ve been looking for more sources and I’ve found http://www.lclabs.co...SAAEgJmOPD_BwE.
I wonder how legit is lclabs.