955 replies to this topic

[resveratrol_guy]

Perhaps the chelating properties of OLE, Longvida and HEPPS are responsible for this major drop in iron stores?

Unless you had a blood donation during this period.

 

That's a compelling hypothesis if we assume that "iron" means "total iron" including that which is bound as hemoglobin. Although, for its part, HEPPS is supposed to be biologically inert apart from its affect on abeta aggregates. It might also have to do with the chelating properties of various juices, particularly grapefruit. There was no blood donation, although the tests themselves took perhaps 15 vials each!

[aribadabar]

That's a compelling hypothesis if we assume that "iron" means "total iron" including that which is bound as hemoglobin. Although, for its part, HEPPS is supposed to be biologically inert apart from its affect on abeta aggregates. It might also have to do with the chelating properties of various juices, particularly grapefruit. There was no blood donation, although the tests themselves took perhaps 15 vials each!

 

Yeah, that should do it - I can confirm that ferritin drops easily 30pts on a single blood donation of 1 pint (and can stay low while hemoglobin remains within normal range). The regular intake of chelators+ the blood test draws probably achieved a similar effect of ~25pts drop of ferritin (which is what I meant by iron stores).

[APBT]

Matt Kaeberlein, Ph.D.: rapamycin and dogs — man’s best friends? — living longer, healthier lives and turning back the clock on aging and age-related diseases (EP.10)

 

https://peterattiamd...mattkaeberlein/

[PAMPAGUY]

Matt Kaeberlein, Ph.D.: rapamycin and dogs — man’s best friends? — living longer, healthier lives and turning back the clock on aging and age-related diseases (EP.10)

 

https://peterattiamd...mattkaeberlein/

 

 

Thanks for posting the Matt Kaeberlein talk on his work with dogs.  As a 72 yo male who has been taking rapa at 6 mg weekly for 24 months, I was most interested in the study on the Doberman in his study.

 

The Doberman had the very beginnings of heart disease that is very prevalent in the breed, and showed the most improvement after taking rapamycin. (appx. 40 min. mark)  On the followup 6 months later, the dog had reverted back to having heart disease after being off of rapa.  Kaeberlein, suggested that he would have kept the dog on rapa for life, until there were negative side effects from the rapa or the dog died.

 

Many people taking rapa do not believe that one has to take it all the time in order to have max effectiveness.  Many would like rapa holidays. (to save money, or other reasons) This is the first I have ever read that suggested that taking rapa continuously seems to be the best course.  It kind of makes sense if your think about it.  Once TOR is no longer inhibited, then all the benefits of a reduced TOR signal are up for grabs.  Such as reduced cancer, heart disease, enhanced immune system, etc.  Until I see a contradictory study, I believe I will continue with the rapa every week until I die. 

[Andey]

Thanks for posting the Matt Kaeberlein talk on his work with dogs.  As a 72 yo male who has been taking rapa at 6 mg weekly for 24 months, I was most interested in the study on the Doberman in his study.

 

The Doberman had the very beginnings of heart disease that is very prevalent in the breed, and showed the most improvement after taking rapamycin. (appx. 40 min. mark)  On the followup 6 months later, the dog had reverted back to having heart disease after being off of rapa.  Kaeberlein, suggested that he would have kept the dog on rapa for life, until there were negative side effects from the rapa or the dog died.

 

Many people taking rapa do not believe that one has to take it all the time in order to have max effectiveness.  Many would like rapa holidays. (to save money, or other reasons) This is the first I have ever read that suggested that taking rapa continuously seems to be the best course.  It kind of makes sense if your think about it.  Once TOR is no longer inhibited, then all the benefits of a reduced TOR signal are up for grabs.  Such as reduced cancer, heart disease, enhanced immune system, etc.  Until I see a contradictory study, I believe I will continue with the rapa every week until I die. 

 

  I recall in this podcast or podcast with David Sabatini that a washout period needed to show an improvement in immune function.

[RWhigham]

 I recall in this podcast or podcast with David Sabatini that a washout period needed to show an improvement in immune function.

Two week washout

From my hearing of the podcast, they only tested immune function  after a two week washout.  So, it's not known if the immune function would have shown the same boost without a washout.

 

Optimum dose

Very interesting is that 5 mg  once-per-week gave the best immune boost and least side effects of the 3 dosing strategies tried. The other two were 20 mg once-per-week and 1 mg daily. 

 

Dog study - heart repair

In the dog study, there was one dog out of five in the high dose group, a Doberman, with incipient left ventricular failure per echogram.  The high dose group received 0.1 mg/kg of rapa MWF for 10 weeks (the low dose group received 0.05 mg/kg). The ejection fraction of the Doberman improved 10% to normal, but six months after stopping the Rapa the incipient failure had returned (a genetically common problem with the Doberman breed).

 

0.1 mg/kg in dog study

The amount of Rapa given with no known side effects to the five dogs in the high dose group was 0.1 mg/kg.  At human weight, a 60 kg subject in the high dose group would have had 6 mg MWF.

 

Peak and Trough for 6 mg MWF

We can calculate the peak and trough using 63 hr for the half life of Rapa in humans. The steady state peak with 48 hr dosing would by 6mg x 1/(1-f), where f is the fraction left after 48 hr. A half life calculator gives f = 0.5897 i.e. 0.5897 of the starting dose remains after 48 hr. Calculating:  1/(1-0.5897) = 2.44.  2.44 x 6 mg = 14.6 mg peak in steady state with 48 hr dosing and 14.6 - 6 mg = 8.62 mg trough in steady state with 48 hr dosing.  72 hr between doses on weekends would lower these a bit (but not much).

 

Wow--people frequently get some mouth sores when starting out at 5 mg once-a-week. Starting at 2 mg once-a-week and working up may reduce the likelihood of mouth sores. (It worked for me). I would expect 6 mg MWF to be problematic.

 

Peak and Trough for 5 mg once-per-week

5 mg once-per-week (168 hr dosing) gives f = 0.1574.  1/(1-0.1574) = 1.186.  1.186 x 5 mg = 5.93 mg peak in steady state with weekly dosing and 5.93 - 5 mg = 0.93 mg trough in steady state with weekly dosing.

 

TorC1 and TorC2 theory

A partial explanation for Rapa's life extension effect follows: The peak dose must somewhat inhibit TORC1, but TORC2 should not be inhibited. When the Rapa decays to a low enough trough between doses TORC2 will not be inhibited.

 

TORC1 is involved in all anabolic functions such as cell growth, construction of proteins and organelles, etc. If TORC1 were completely inhibited too long cells would waste away, but when TORC1 is inhibited just right, cells will switch to anabolic mode just long enough for cell "house keeping" such as autophagy to clean house improving the cell's health. Presumably intermittent fasting, exercise, and caloric restriction may have similar effects.  Rapa inhibits TORC1 but not completely (else continuous dosing would be deadly).

Edited by RWhigham, 08 September 2018 - 08:34 PM.

[RWhigham]

 

 

"cells will switch to anabolic mode"

Misspoken. Should be "cells will switch to catabolic mode" when TOR1 is inhibited.

Edited by RWhigham, 08 September 2018 - 10:45 PM.

[PAMPAGUY]

Here is a breakdown of Dr. Attia's podcast with Joe Rogan. Including the proper dose and dosing schedule for rapa. (Under Diet and Nutrition section)    http://podcastnotes..../04/27/attia-2/

Edited by PAMPAGUY, 09 September 2018 - 06:33 AM.

[NeuroGeneration]

A few novice questions I was hoping some of your could give your thoughts on:

 

1. If rapamycin reduces TORC1 and by extension, cellular growth, how likely is it that this results in inadequate repair? For example, you exercise hard or go out in the sun and have dermal sun damage, and the body can't keep up with repairing the damage. Could this lead to the accumulation of senescent cells (thus, a long-term negative)? Along this line of thought, is it best to be cautious while dosing rapamycin, and to the best of our abilities only engage in activities that may cause cellular damage when we're approaching the trough?

 

2. Does anyone have any experience with or knowledge of rapamycin in regards to autoimmunity? I got a comprehensive blood panel done and learned I have some anti-GAD antibodies, which in a minority of cases, can lead to type-1 diabetes. I'd like to reduce my risk (and those antibodies) by as much as possible, and thought that rapamycin might help.

 

3. What's everyone's experience with rapamycin and muscle growth vs. atrophy? Ideally, people who already worked out and had muscle: did it increase, decrease or stagnate? Any comments on changes to workout routines (i.e., people often speak of having more energy with rapamycin) would be helpful.

 

4. Any libido changes?

[Razor444]

2. Does anyone have any experience with or knowledge of rapamycin in regards to autoimmunity?

 

I've got ulcerative colitis, and rapa helps the symptoms.

[RWhigham]

 

2. Does anyone have any experience with or knowledge of rapamycin in regards to autoim

I've got ulcerative colitis, and rapa helps the symptoms.

• Improved immune function is expected from rapamycin since 5 mg once-per-week was demonstrated to boost the immune response to vaccination in old people with poor immune systems
• Razor444 Please look up zinc-L-carnosine, I think it might help with your gastric problem.  It is reputed to repair gut mucosa, stop gut leakage, and cure acid reflux
• My wife's alopecia areata went into remission (stopped immediately) when she started taking homemade C60_EVOO. We took 1 tsp containing 3 mg of C60 3x per week (MWF). Also, my allergic reaction to a medication (all-over hives) stopped immediately (I continued the medication with no further problem)

Zinc-L-Carnosine

Zinc-L-carnosine is a pharmaceutical in Japan but is sold as a supplement in the U.S.  It comes in 75 mg capsules. They specify 75 mg twice per day on an empty stomach.  Do not combine with food or you may get a copper deficiency. Long term 1 capsule per day gives the RDA for zinc. Additional zinc in a multi-vitamin and mineral might cause copper deficiency. 2 capsules per day long term might cause copper deficiency

 

Copper

Cocoa, cashew nuts, and oysters are highest in biological copper. The copper from pipes and that put into supplements is not biologically compatible and likely toxic. The copper in food is in a biological form that is not available in a supplement. [Sorry, I cannot at the moment find the scientific article where I read this. As I recall, it has to do with the charge + or ++ of the released copper. The chemistry was over my head] 

 

Zinc

I took a single capsule of zinc-picolinate containing 20 mg of zinc with lunch and no other zinc; and after a while, I tested low for serum copper. I was taking the zinc-picolinate with food because most zinc supplements can cause queasiness on an empty stomach. Zinc-L-carnosine does not. Zinc interferes with the absorption of copper from the gut.

 

C60_EVOO

I think it's not safe to buy this from a commercial supplier. It must not be exposed to light. A dose of the C60_EVOO that Kelsey Moody exposed to intense light caused his mice to all die overnight. You should learn to make it yourself.  I use recent harvest pristine olive oil (De Carlo) sold in a light tight tin, and I use 99.95% pure C60. You need a magnetic stirrer. I stir it in a wine bottle with a narrow neck so not much oxygen is left under the cork, and wrap it with tin foil to keep out the light.

 

Rapamycin

I believe 5 mg per week of rapamycin has stimulated my immune system to finally get rid of some bacteria that were embedded deeply in the skin on my face and fingers and caused fulminating eruptions periodically for over 30 years.

 

Edited by RWhigham, 21 September 2018 - 12:58 AM.

[Razor444]

 

• Improved immune function is expected from rapamycin since 5 mg once-per-week was demonstrated to boost the immune response to vaccination in old people with poor immune systems
• Razor444 Please look up zinc-L-carnosine, I think it might help with your gastric problem.  It is reputed to repair gut mucosa, stop gut leakage, and cure acid reflux
• My wife's alopecia areata went into remission (stopped immediately) when she started taking homemade C60_EVOO. We took 1 tsp containing 3 mg of C60 3x per week (MWF). Also, my allergic reaction to a medication (all-over hives) stopped immediately (I continued the medication with no further problem)

Zinc-L-Carnosine

Zinc-L-carnosine is a pharmaceutical in Japan but is sold as a supplement in the U.S.  It comes in 75 mg capsules. They specify 75 mg twice per day on an empty stomach.  Do not combine with food or you may get a copper deficiency. Long term 1 capsule per day gives the RDA for zinc. Additional zinc in a multi-vitamin and mineral might cause copper deficiency. 2 capsules per day long term might cause copper deficiency

 

Copper

Cocoa, cashew nuts, and oysters are highest in biological copper. The copper from pipes and that put into supplements is not biologically compatible and likely toxic. The copper in food is in a biological form that is not available in a supplement. [Sorry, I cannot at the moment find the scientific article where I read this. As I recall, it has to do with the charge + or ++ of the released copper. The chemistry was over my head] 

 

Zinc

I took a single capsule of zinc-picolinate containing 20 mg of zinc with lunch and no other zinc; and after a while, I tested low for serum copper. I was taking the zinc-picolinate with food because most zinc supplements can cause queasiness on an empty stomach. Zinc-L-carnosine does not. Zinc interferes with the absorption of copper from the gut.

 

C60_EVOO

I think it's not safe to buy this from a commercial supplier. It must not be exposed to light. A dose of the C60_EVOO that Kelsey Moody exposed to intense light caused his mice to all die overnight. You should learn to make it yourself.  I use recent harvest pristine olive oil (De Carlo) sold in a light tight tin, and I use 99.95% pure C60. You need a magnetic stirrer. I stir it in a wine bottle with a narrow neck so not much oxygen is left under the cork, and wrap it with tin foil to keep out the light.

 

Rapamycin

I believe 5 mg per week of rapamycin has stimulated my immune system to finally get rid of some bacteria that were embedded deeply in the skin on my face and fingers and caused fulminating eruptions periodically for over 30 years.

 

 

I've tried all those things. Thanks for the suggestions, though. I'm always looking to add to my stack.

[bladedmind]

I'm 69 years old, APOE 4/4 and interested in the 6 mg/week rapamycin regime.  I tried cautiously for several weeks, then laid off because of feeling sick for unknown reasons (general health excellent).  Two weeks after last rapamycin I was struck with acute pericarditis (my heart health is otherwise excellent).  Took three months of medication to prevent recurrence.  

 

Was considering taking up rapamycin again, but still feeling mildly sick and a series of new symptoms (among them dry eyes, fatigue, sweating) prompted testing for Sjogren's.  It does appear that I have mild and early primary Sjogren's syndrome.  

 

I don't have biochemistry or medical training, and it's unclear to me whether the rapamycin regime would make Sjogren's worse, better, or do nothing at all.  Recent entries above discuss the autoimmunity question.  One person says rapamycin helps ulcerative colitis.  Another says it stimulates the immune system.  But isn't hyperactive stimulation of the immune system the cause of autoimmunity diseases?   I wondered whether the pericarditis might have been triggered by the rapamycin.  

 

It appears that not much can be done to mitigate Sjogren's.  

 

Thanks for hearing me out.  

 

[MikeDC]

https://www.ncbi.nlm...les/PMC3344911/

Low dose Rapamycin make autoimmune diseases worse. High dose is beneficial.

[Valijon]

Im going to do something Ive never done before. Mike, I thank you for this information. Ill stick with metformin and Berberine and hold off on Rapamycin. Ill continue to monitor this drug. About the C60oo. I must agree with this. I used about 15ml of it until I threw it out. Many substances we are using could use a lot more investigating.

The question about Rapamycin effecting hypertrophy or causing atrophy are still unanswered.

Edited by Valijon, 22 October 2018 - 12:37 AM.

[smithx]

Both dosing regimens in this study were DAILY dosing. What people are doing mostly here is weekly or even less-frequent dosing which very much changes the immune effects of the drug.
 

https://www.ncbi.nlm...les/PMC3344911/
 
we treated B10.RIII mice with intraperitoneal injection of 1.5 or 7.5 µg rapamycin daily

[bladedmind]

Both dosing regimens in this study were DAILY dosing. What people are doing mostly here is weekly or even less-frequent dosing which very much changes the immune effects of the drug.
 

 

Yes, thank you.  What is known, or can be inferred, about the negative or positive effects of weekly or so rapamycin on those with autoimmune diseases, in general, or for specific such diseases?  

[QuestforLife]

Given that rapamycin is dosed weeky because of it's long half life - and that the aim is to inhibit mTOR strongly, but not for very long - and also given the shorter half-life everolimus will not be off patent for a few more years, has anyone tried upregulating CYP3A4?  

 

For example taking St John's Wort 12 hours after rapamycin to ensure it is rapidly cleared. Might also allow you to take a higher dose of rapamycin, without the side effects. There are some other ideas here:

 

https://en.wikipedia.org/wiki/CYP3A4

 

I normally feel tired on the 2nd-3rd day after rapamycin, which is at about the 1 half-life mark. Probably due to suppressed cell proliferation. So it would be interesting to see if a CYP3A4 agonist would change that. 

Edited by QuestforLife, 01 November 2018 - 09:31 AM.

[ceridwen]

I think that Rapamycin also increases the strength of other meds taken with it. Or so Dr Green said
I would be interested as I also have at least one autoimmune disease

[Andey]

 

 

I normally feel tired on the 2nd-3rd day after rapamycin, which is at about the 1 half-life mark. Probably due to suppressed cell proliferation. So it would be interesting to see if a CYP3A4 agonist would change that. 

 

 

Do you measure HRV? it would be interesting to see how those tiredness periods correlate with objective measurements.

[QuestforLife]

Do you measure HRV? it would be interesting to see how those tiredness periods correlate with objective measurements.

 

No, but that shouldn't be too hard so I will look into it.

[TaiChiKid]

Here is a recent post on Rapamycin:  https://onlinelibrar...1111/acel.12882

 

LinL  :  http://onlinelibrary...acel.12882/epdf

[malbecman]

Here is a recent post on Rapamycin:  https://onlinelibrar...1111/acel.12882

 

LinL  :  http://onlinelibrary...acel.12882/epdf

 

 

 Thanks for the post, interesting paper.  Just to point out, this study used continuous/ad libitum feeding of rapamycin in the diet.  Most people dosing

rapamycin have settled on intermittent dosing.

[aribadabar]

Guys,

 

what is your take on Rapamycin's dual and conflicting action : 1) as an inhibitor of mTOR - a major pathway involved in angiogenesis and cancer proliferation and 2) Immunosuppressant which may impede the innate defence of the body against cancer.

 

Do you consider Rapamycin to be net positive or negative in either 1) cancer prevention and 2) as an adjunct to chemotherapy?

[smithx]

Read these:

 

https://www.ncbi.nlm...les/PMC4717280/

https://www.research...le_C57BL6J_Mice

 

This is why most people here are taking it weekly or even less frequently (I do every 9 days).

 

Guys,

 

what is your take on Rapamycin's dual and conflicting action : 1) as an inhibitor of mTOR - a major pathway involved in angiogenesis and cancer proliferation and 2) Immunosuppressant which may impede the innate defence of the body against cancer.

 

Do you consider Rapamycin to be net positive or negative in either 1) cancer prevention and 2) as an adjunct to chemotherapy?

 

[aribadabar]

Read these:

 

https://www.ncbi.nlm...les/PMC4717280/

https://www.research...le_C57BL6J_Mice

 

This is why most people here are taking it weekly or even less frequently (I do every 9 days).

 

Thank you for the pointers.

 

They cover the prevention scenario somewhat but say nothing about being positive or negative added to a chemo protocol in an existing cancer situation.

Would you share your thoughts on that ?

[smithx]

This is purely speculation on my part, since I have no medical degree, so please don't rely on it in anyway.

 

I think that if rapamycin protects cells and helps to keep them from becoming senescent, it could potentially interfere with chemotherapy by protecting the cancer cells.

 

On the other hand it could kill them but I don't know. Best to do some literature searches!

 

 

Thank you for the pointers.

 

They cover the prevention scenario somewhat but say nothing about being positive or negative added to a chemo protocol in an existing cancer situation.

Would you share your thoughts on that ?

 

[VP.]

Dr. Peter Attia has started taking Rapamycin.

So why not just take rapamycin every day?

• Peter says the following 3 things need to be true, if you’re taking the correct dose of rapamycin:
  • Glycemic response will be unchaged or improved (it shouldn’t get worse, which could happen if you take too much rapamycin)
  • Immunity should get better, not worse
  • Autophagy should increase (but there’s currently no way to measure this)
• One of the most obvious negative side effects of rapamycin is mouth sores (apthous ulcers) – Peter equates them to “super annoying canker sores”

What would be the correct rapamycin dosing?

• In the Mannick study, the negative side effects when taking 5 mg of rapamycin once per week, compared to taking 1 mg every day, didn’t seem to be that much worse
  • But taking 20 mg once per week vs. 5 mg once per week, showed no additional immune benefit (however there were more negative side effects)
• Matt Kaeberlein has done some studies on dogs, suggesting the optimal dosing in humans would be around 4-8 mg, in some sort of pulsatile/episodic fashion (every other day or every third day)
  • Why? – You don’t want to inhibit MTORC2 
    • If you dose with rapamycin every day, you don’t allow for TOR to be recirculated, and within a few days of consecutive dosing, you start to inhibit the creation of mTORC2
• So in short, there’s no side effects to taking too little (just a lack of benefit), but you want to be careful about taking too much
• If Peter were to guess the perfect dose: 4-6 mg every 4-7 days

Rapamycin Appears to Inhibit Senescent Cells

• Senescent cells are cells which are “basically bad actors”
  • They essentially mimic other types of cells, with a less effective version
  • So inhibiting them, would be a benefit

Can anyone take rapamycin?

• Yes – all you need is a presrciption from your doctor
  • We just need more data to indicate that we’re not taking too much/we’re taking enough

Does Peter take rapamycin?

• Yes (for the last 3 months), but he’s never written a prescription for it
  • “I’m relatively confident that the dosing I’m using is relatively congruent with all the data I’ve assimilated over the past 4 years, and speaking with some of the smartest people in the world”
  • He’s taking 5 mg (he doesn’t say how often)
• Why does he take it?
  • “For me and my risk appetite, I think the risk of not taking it is higher than the risk of taking it”
  • A good way to think about this – “Strong convictions loosely held”
    • Peter says, given new information/data, he’d be apt to change his mind very easily
• Has he noticed anything?
  • For the first two months, he had very bad mouth sores…and then they stopped
  • Nothing else
• Here’s what Peter has learned from a physician, also in NY, who regularly prescribes rapamycin – “the worse your glucose levels are starting out, the more of an improvement you can get”
  • What else is this doctor seeing? 
    • Patients are losing weight, their triglycerides are falling, insulin/glucose levels are improving as well as HA1c

Are there any cognitive benefits of taking rapamycin?

• “It’s a bit too soon to say”
  • Peter says it’d be a very interesting research question – What happens when you give rapamycin to people in the very early stages of cognitive decline?
  • “There’s definitely preliminary data that suggests, in certain models, that rapamycin is delaying the onset of cognitive impairment”

 

https://podcastnotes.../01/17/attia-5/

[Valijon]

Is anyone taking Metformin with their Rapamycin? If so, what subjective changes have you noticed? I know Rocket works out, other members must also. Is Rapamycin hindering hypertrophy in any way? After all the trauma Ive suffered the last few years, I went back to powerlifting and I dont want to decrease strength gains by taking Rapamycin.

[VP.]

Is anyone taking Metformin with their Rapamycin? If so, what subjective changes have you noticed? I know Rocket works out, other members must also. Is Rapamycin hindering hypertrophy in any way? After all the trauma Ive suffered the last few years, I went back to powerlifting and I dont want to decrease strength gains by taking Rapamycin.

 

Tomorrow will be the two-year anniversary of my taking rapamycin/metformin. I never liked lifting but I started in March of last year after hearing about the dangers of muscle loss in aging. I now can lift more than I ever had before but still nothing to brag about. I think rapamycin gave me the energy to stick with a lifting program but that's all subjective. 58 years old.