955 replies to this topic

[Benko]

Most Indian drug companies are reliable? What makes you say that?

https://www.google.c...rugs-from-india

[PAMPAGUY]

http://www.pharmalea...ompanies-india/

[smithx]

http://www.pharmalea...ompanies-india/

Biocon, the brand of this rapamycin, is on the list you linked, but Swiss Garnier, the actual manufacturer, isn't.

[PAMPAGUY]

Google the company. There are probably 300 companies that sell manuf. Rapa. Have ordered rapa from dropshipmd.com and have been pleased with the rapa regardless of the brand name.. All rapa sold in Canada comes from India. If really worried pay $3.25 mg from Canada.

[Skyguy2005]

Hi Smithx,

 

Or you can go the easy route and dose too high?

I found out mine was real. Instead of taking 9mg I took 12mg.

I got a very large and painful canker sore on my tongue.

To me that's as good a confirmation as it gets that it's REAL lol.

 

Cheers,

 

DareDevil

 

How's the taste?

[smithx]

Google the company. There are probably 300 companies that sell manuf. Rapa. Have ordered rapa from dropshipmd.com and have been pleased with the rapa regardless of the brand name.. All rapa sold in Canada comes from India. If really worried pay $3.25 mg from Canada.

Typically Canadian pharmacies seem to require a prescription, and I don't think my doctor would give me one for rapamycin without a lot of discussion. Or do you know of some which don't require it?

[PAMPAGUY]

Order from dropshipmd.com and they will send you real rapa regardless of the brand.

[PAMPAGUY]

New trial results on mTor inhibition via Rapa and other inhibitors.  Treatment of diseases and ageing.  Very good speaker, very knowledgeable.

NAC is major mTor inhibitor.

 

[to age or not to age]

my wife and I have taken rapamycin since last January, she, 3mg once a week, me 5 mg once  per week.  I cut back to 5mg every 10 days two months ago.

She was experiencing recurring mouth sores and stopped a couple months ago.  Her health since has b been excellent. It may be that rapamycin should be taken 

intermittently for a period off time, then stopped, much like the experiment with the mice, so as to avoid a build up of it in your system. Given that it has a half life of 60 hours,

it is possible that over a year or so, it does build up, albeit slowly. I have just discontinued it.  Two week ago, I took it late on Wednesday, and caught a flu on friday.  This is the first time I had been sick with anything in 10 years.  Felt like a perfect storm of immune system getting knocked down a bug.  

[RWhigham]

Given that it has a half life of 60 hours,

it is possible that over a year or so, it does build up, albeit slowly. I have just discontinued it.

For repeated doses at a fixed interval

• Let x = Amt at end of interval / Amt at start of interval
• Find x from any half life calculator by putting in 1 for the initial dose and the half-life and dose interval.
• The steady state peak then is 1/(1-x) higher than for a single dose
• The steady state trough then is x times the steady state peak

Derivation:: 

For simplicity normalize the dose to 1.

After the 1st dose we have 1. After the 2nd dose we have (1+x), After 3rd dose 1+x(1+x)  after the 4th dose we have 1+x[1+x(1+x)] = 1 + x + x^2 + x^3.  After the (n+1)th dose  we have 1 + x + x^2 + x^3 +... x^n  .=def  S

S-xS = 1 - x^(n+1)  for x < 1 x^(n+1) -> 0 for large n, so  S(1-x) -> 1 for large n giving S= 1/(1-x) in steady state

 

Example #1 - 5 mg every 7 days (168 hrs) with half-life of 60 hrs, the half life calculator gives x =  0.14358729437463

Steady state peak = (5 mg)(1/(1-0.14) ) = 5 mg/0.86 = 5.8 mg  and  steady state trough = (0.14)(5.8 mg) = 0.81 mg

 

Example #2 - 5 mg of rapamycin every 10 days (240 hrs) the half life calculator gives x =  0.0625,

   Steady state peak = (5 mg)(1/(1-0.06) ) = 5 mg/0.94 = 5.33 mg  and steady state trough = (0.06)(5.33 mg) = 0.32 mg

 

Edited by RWhigham, 14 December 2017 - 10:55 PM.

[maxwatt]

New trial results on mTor inhibition via Rapa and other inhibitors.  Treatment of diseases and ageing.  Very good speaker, very knowledgeable.

NAC is major mTor inhibitor.

 

What dose?  Is there a link to the paper?

Edited by maxwatt, 15 December 2017 - 01:49 AM.

[aribadabar]

 

New trial results on mTor inhibition via Rapa and other inhibitors.  Treatment of diseases and ageing.  Very good speaker, very knowledgeable.

NAC is major mTor inhibitor.

 

What dose?  Is there a link to the paper?

 

4800mg/d.

 

https://www.ncbi.nlm...les/PMC3411859/

[StanG]

My experience with RAPA so far:

 

I'm 5'9" tall and weigh 138lbs so I don't want to lose weight. I've been taking about 6mg of RAPA weekly for about 3 months now. I do a number of things to try and live the longest healthspam possible including eating well. However, since starting to take RAPA, I've had to eat more "junk food" which I ate very little of before, just to maintain my weight. Since it is the holiday season I'm having lots of food and I continue to eat the same amount of healthy food as I did before. While many of you would like this problem, I don't. I weighed 197lbs 42 years ago (I'm 74 now) when I decided to change my life and I've kept at it. 

 

Have a happy holiday season and a happy and healthy 2018!

[maxwatt]

at 138 pounds, your BMI is 20.2, which is in the normal healthy range.   you would have to drop about 20 pounds to bring your BMI below 18, considered underweight.  Even that may still be healthy, BMI figures are skewed to overweight Americans. 

If hunger is not unbearable, perhaps you can skip the junk and see where your weight stabilizes.

[StanG]

Thanks Maxwatt and I agree. My wife gives me a hard time even at this weight because when I met her 42 years ago, I weighed 197. It took me quite awhile but I finally got her on a two day, 500 calorie healthy diet and her weight went down from (she says 225 but I think it was more( to 146 where she keeps it). She's bought all sorts of new cloths in the last 5 years and I'm always telling her how good she looks (which she does) (and not asking what they cost). What I don't tell her is how much healthier I believe she's gotten. 

 

My doctor likes to call me "skinny" and says he'd like to clone me (one of me still eating the way I used to way back when and the real me). At 74 years of age all my tests are in the normal range and I take no medications for illnesses only to prevent them.

 

I can't wait for really upstream solutions and I'm taking a few things that are somewhat upstream.

 

I wish everyone a happy and healthy 2018!

[TaiChiKid]

After my stint of two doses of D&Q, I began trying the rapamycin protocol in this fashion:  I began Aug 6/2017 at 5 mg weekly until oct 22nd whereupon I took 5 mg every two weeks.  I will continue this protocol until late January this year, where upon I will stop for a period of one year, and then repeat yearly.  I also take 500 mg metformin daily, which I have been doing for about 20 years or so (No, I am not diabetic..)  I will continue the daily metformin.  I reckon that the types of senolytic cells which are killed by this pathway will be mostly wiped out by the end of my protocol, hence the transition to once yearly.  I feel mostly more energy, but then I have always been thin

 

I have been studying and practising anti-aging techniques for 50 years as of 2018 (just a few years before Dirk and Sandy, who were still at university), but only began keeping a detailed log the past twenty years or so.  I wish I had gone to MIT as I would have met Dirk since I had won a full scholarship to go there. Instead I went into honours pre-med at my local university.  I am very glad to have found this forum a couple of years ago, and the comments of the very knowledgeable members here.

 

I look forward to other senolytics such as FOXO4-DR1!

 

One thing I wonder about is:  'How do you know when you are close, very close to getting 'there'??"

[TaiChiKid]

Another recent study for intermittent use:  Short-term low-dose mTORC1 inhibition in aged rats counter-regulates age-related gene changes and blocks age-related kidney pathology
Tea Shavlakadze Jiang Zhu Sharon Wang Weihua Zhou Bret Morin Marc A Egerman Lin Fan Yanqun Wang Oleg Iartchouk Angelika Meyer ... Show more
The Journals of Gerontology: Series A, glx249, https://doi.org/10.1093/gerona/glx249
Published:03 January 2018

 

Abstract

Rapalogs, inhibitors of mTORC1 (mammalian target of rapamycin complex 1), increase lifespan and delay age-related phenotypes in many species. However the molecular mechanisms have not been fully elucidated. We determined gene expression changes comparing 6 and 24-month old rats in the kidney, liver and skeletal muscle, and asked which of these changes were counter-regulated by a clinically-translatable (short-term and low-concentration) treatment, with a rapalog (RAD001). Surprisingly, RAD001 had a more pronounced effect on the kidney under this regimen in comparison to the liver or skeletal muscle. Histologic evaluation of kidneys revealed that the severity of chronic progressive nephropathy lesions was lower in kidneys from 24-month old rats treated with RAD001 compared with vehicle. In addition to other gene expression changes, c-Myc, which has been shown to regulate aging, was induced by aging in the kidney and counter-regulated by RAD001. RAD001 caused a decrease in c-Myc protein, which could be rescued by a proteasome inhibitor. These findings point to settings for use of mTORC1 inhibitors to treat age-related disorders, and highlight c-Myc regulation as one of the potential mechanisms by which mTORC1 inhibition is perturbing age-related phenotypes.

[PAMPAGUY]

Have been on rapa for 1 year.  My creatine  has dropped from 1.2 to .85.  That is really good.  BPH also improved.  Arthritis in right hip has almost disappeared.  71 yo. male

[Hip]

As a ballpark figure, I worked out (very roughly) that 1 in 5 patients taking rapamycin for 5 years might be expected to develop diabetes as a result. See this post.

Edited by Hip, 09 January 2018 - 11:46 PM.

[RWhigham]

As a ballpark figure, I worked out (very roughly) that 1 in 5 patients taking rapamycin for 5 years might be expected to develop diabetes as a result. See this post.

If and only if 5 mg is taken daily. Hopefully there are no such idiots taking rapamycin for life extension.   (See Blagosklonny for life extension with rapalogs)

Edited by RWhigham, 10 January 2018 - 12:03 AM.

[VP.]

It's been almost one year since I started metformin at 1000mg a day and Rapamycin, about 5mg a week. My new blood tests are in and look fine. Glucose went from 98 to 89 mg/dL. Creatinine pre: 0.9 post: 1.0. Cholesterol/LDL pre: 3.33 post: 2.73. All due to an increase in HDL from 72 to  88. Triglycerides pre: 86 post: 137 mg/dL. (not good) Testosterone pre: 616 post: 719. Free testosterone  test pre: 8.7 post: 9.0 ng/dL. Using Aging AI 2.0 from Insilico Medicine my age dropped from 39 last year to 31 this year for whatever that's worth (I'm 57). I lost about 9 pounds from 186 to 177lbs. (6'2') I was sick once this year in March. All in all I am happy with how I feel and will continue my protocol. 

http://www.aging.ai/

 

Edited by VP., 14 January 2018 - 07:11 PM.

[VP.]

I made a mistake in my last post. My Triglycerides went DOWN, not up, from 137 to 86. That's very good. 

[VP.]

Major redo. I made a serious mistake by using the wrong units for Globulin, one of the most important values in the age calculator. Please use care in entering the data. I used g/dL instead of mg/dL. My new estimated age is 50 and last years was 46! Small changes make a big difference in the calculations. 3 years was added to my age because my Na levels went from 139 to 142 meq/dL. One year added due to ALT going from 30 to 26 U/L. One year added due to Albumin going from 4.7 to 4.6 g/dL. The Mean Absolute Error for the test is 6.2 years so it is what it is. Here is the reference study. Done on Russians who tend not to be very healthy. https://www.ncbi.nlm...pubmed/27191382

[Michael]

I would ignore whatever aging.ai churns out, even if you have all the analytes and enter them in on the proper scale. There are no data to support its function as a biological age score; the mean absolute error for getting even chronological age within a 10-year frame is about six years; and it gives wildly different results in different populations.

[sthira]

Yeah aging.ai told me I'm still a zygote, so I retook it with my gf's numbers, evidently she's putrefying.

[aribadabar]

Major redo. I made a serious mistake by using the wrong units for Globulin, one of the most important values in the age calculator. Please use care in entering the data. I used g/dL instead of mg/dL. My new estimated age is 50 and last years was 46! Small changes make a big difference in the calculations. 3 years was added to my age because my Na levels went from 139 to 142 meq/dL. One year added due to ALT going from 30 to 26 U/L. One year added due to Albumin going from 4.7 to 4.6 g/dL. The Mean Absolute Error for the test is 6.2 years so it is what it is. Here is the reference study. Done on Russians who tend not to be very healthy. https://www.ncbi.nlm...pubmed/27191382

 

I agree with the other posters above - the sensitivity of this AI test is too low to draw any conclusions.

If anything, lower ALT number is an indication of better liver function, not worse.

Edited by aribadabar, 15 January 2018 - 11:43 PM.

[Razor444]

Yeah aging.ai told me I'm still a zygote, so I retook it with my gf's numbers, evidently she's putrefying.

 

On the positive side: at least you weren't a gamete!

[VP.]

Is this why Glucosamine has anti aging effects? https://www.scienced...40408122135.htm

 

In the recently published study (2014) that was performed at ETH Zurich and four German research institutions, Ristow and his colleagues applied glucosamine to roundworms and found that they live around 5% longer than their untreated counterparts.

Next and most importantly, the researchers fed glucosamine to aging mice in addition to their normal diet. The mice were 100 weeks of age, reflecting a comparative human age of approximately 65 years. A control group of mice received no glucosamine while otherwise receiving an identical diet. Feeding the supplement to mice extended their lifespan by almost 10%, reflecting around 8 additional years of human lifespan. Moreover, glucosamine improved glucose metabolism in elderly mice indicating protection from diabetes, a life-threatening disease most prevalent amongst the elderly.

 

New study: https://www.ncbi.nlm..._medium=twitter

Glucosamine promotes osteoblast proliferation by modulating autophagy via the mammalian target of rapamycin pathway.

Glucosamine is effective in the treatment of osteoarthritis; however, its effect on osteoporosis remains unclear. Decreased activity of osteoblasts is the main cause of osteoporosis. Here, we examined the effects of glucosamine on osteoblasts. The potential underlying mechanisms were explored. The results showed that glucosamine had a biphasic effect on the viability of hFOB1.19 osteoblasts. At low concentrations (<0.6 mM), glucosamine induced hFOB1.19 cell proliferation, whereas at high concentrations (>0.8 mM) it induced apoptosis. The autophagy inhibitor 3-methyladenine (3-MA) was used to verify that glucosamine modulated hFOB1.19 cell viability via autophagy. The induction of apoptosis by high concentrations of glucosamine was significantly exacerbated by 3-MA, whereas the promotion of cell proliferation by low concentrations of glucosamine was significantly suppressed by 3-MA. Autophagy was examined by western blot detection of autophagy-related proteins including LC3, Beclin-1, and SQSTM1/p62 and by immunofluorescence analysis of autophagosomes. Glucosamine activated autophagy in a time- and concentration-dependent manner. Investigation of the underlying mechanism showed that glucosamine inhibited the phosphorylation of m-TOR in a concentration-dependent manner within 48 h, and rapamycin significantly inhibited the phosphorylation of m-TOR. These results demonstrated that glucosamine promoted hFOB1.19 cell proliferation and increased autophagy by inhibiting the m-TOR pathway, suggesting its potential as a therapeutic agent for osteoporosis.

 

Edited by VP., 18 January 2018 - 06:02 AM.

[Michael]

 

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.

India appears to be a particularly risky place to source generic drugs

[maxwatt]

There are two issues to ordering drugs out of India.

 

First, the vendors may cheat, with counterfeit of expired medications. 

Second, as Michael's link pointed out, the reliability of the manufacturers in India may be questionable.

 

We have a forum on Retailers/product discussion where this may be addressed.