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New Rapamycin Study- up to 60% increase in mouse lifespan- Anyone Experimenting With This?

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#631 QuestforLife

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Posted 17 June 2018 - 06:31 PM

You've not got that quite right - you don't get insulin resistance from rapamycin, you get glucose intolerance. Not quite the same thing. It is like your body thinks you are starving, so your peripheral tissues forgo glucose to save it for the brain. So you will not get more insulin in your blood, but you will get more glucose.

I personally think the raised glucose is benign, and mine is still in the normal range, so I don't bother with Metformin or anything like that.
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#632 Andey

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Posted 17 June 2018 - 06:50 PM

You've not got that quite right - you don't get insulin resistance from rapamycin, you get glucose intolerance. Not quite the same thing. It is like your body thinks you are starving, so your peripheral tissues forgo glucose to save it for the brain. So you will not get more insulin in your blood, but you will get more glucose.

I personally think the raised glucose is benign, and mine is still in the normal range, so I don't bother with Metformin or anything like that.

 

Could be because I could still measure that I am in ketosis or just a bit below it while having a spike of glucose. I 've seen this before only after exercise. Fasting levels are completely ok.

 



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#633 Jaris

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Posted 17 June 2018 - 07:50 PM

Hello, do you have any source that support this dosage ? I'm 22 and just want to avoid cancer

 

Actually, this is a bit off topic, but since you asked about cancer, here's a video that gives the top recommendations for cancer prevention. 


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#634 VP.

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Posted 18 June 2018 - 05:05 PM

What is the current consensus on insulin resistance induced by rapamycin?

 

Ive actually took my first 5mg Everolimus this week.  Nothing to write about, the only thing that I noticed is an increased lymphatic load in the neck region for 2 days post-pill like I was having some flu. 

I check my BG quite often because I am trying to get max number of summer fruits without falling out of ketosis for too long and my BG spikes became way higher than usual. I could just cut out carbs more but dont like the thought that my insulin is probably way higher now because of induced resistance.

Is it a best practice to take something like metformin while taking rapamycin like drugs or just don't bother with it?

 

A study just came out addressing that issue. 

Rapamycin improves insulin resistance and hepatic steatosis in type 2 diabetes rats through activation of autophagy

https://onlinelibrar...1002/cbin.11015


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#635 MikeDC

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Posted 18 June 2018 - 05:47 PM

A study just came out addressing that issue. Rapamycin improves insulin resistance and hepatic steatosis in type 2 diabetes rats through activation of autophagy
https://onlinelibrar...1002/cbin.11015


Rapa is much less effective than Metformin.
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#636 Andey

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Posted 18 June 2018 - 05:53 PM

A study just came out addressing that issue. 

Rapamycin improves insulin resistance and hepatic steatosis in type 2 diabetes rats through activation of autophagy

https://onlinelibrar...1002/cbin.11015

 

Thank you

It also looks like body needs some adaptation period and some studies could report negative consequence because of short duration

https://www.ncbi.nlm...les/PMC3658445/

Here we show that detrimental effects of rapamycin treatment were only observed during the early stages of treatment. As the treatment continued for 20 weeks, these effects were reversed or diminished; the mice had better metabolic profiles, increased oxygen consumption and ketogenesis, and markedly enhanced insulin sensitivity.

Mice, but anyway

 

Sorry for noob`s question again but is it possible to gain muscle mass while taking rapamycin or everolimus intermittently? Anecdotal data is welcomed)



#637 VP.

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Posted 18 June 2018 - 09:17 PM

Thank you

It also looks like body needs some adaptation period and some studies could report negative consequence because of short duration

https://www.ncbi.nlm...les/PMC3658445/

Here we show that detrimental effects of rapamycin treatment were only observed during the early stages of treatment. As the treatment continued for 20 weeks, these effects were reversed or diminished; the mice had better metabolic profiles, increased oxygen consumption and ketogenesis, and markedly enhanced insulin sensitivity.

Mice, but anyway

 

Sorry for noob`s question again but is it possible to gain muscle mass while taking rapamycin or everolimus intermittently? Anecdotal data is welcomed)

I have not lost any muscle in the 17 months I've been on Rapa. I do believe you should not lift 3 days after dosing because of the 62 hour half life. Everolimus has a 30 hour half life so that would be less restricting. 


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#638 smithx

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Posted 19 June 2018 - 05:58 AM

Ive actually took my first 5mg Everolimus this week. 

 

Where did you get it and what did it cost?

 

Metformin is thought by some to be a good thing to take with rapamycin.



#639 Andey

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Posted 19 June 2018 - 07:12 AM

Where did you get it and what did it cost?

 

Metformin is thought by some to be a good thing to take with rapamycin.

 

Locally, there are a lot of drugs that are not registered in Ukraine and people bring them from India semi-legally. Being an anticancer drug that is way cheaper than branded Afinitor helps availability.

10mg*10 Cipla Rolimus brand for something around $162. I divide tablet in half.

 

It costs about 30% less in India https://www.1mg.com/...g-tablet-334115


Edited by Andey, 19 June 2018 - 07:15 AM.


#640 Nate-2004

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Posted 19 June 2018 - 12:58 PM

Locally, there are a lot of drugs that are not registered in Ukraine and people bring them from India semi-legally. Being an anticancer drug that is way cheaper than branded Afinitor helps availability.

10mg*10 Cipla Rolimus brand for something around $162. I divide tablet in half.

 

It costs about 30% less in India https://www.1mg.com/...g-tablet-334115

 

Considering this but probably not worthwhile till I'm 50 no? I'm 44 now.



#641 Andey

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Posted 19 June 2018 - 02:10 PM

Considering this but probably not worthwhile till I'm 50 no? I'm 44 now.

 

I am a similar age. To be honest, Ive started to take it not so much for anti-aging benefits, but to fix my messed up immune system.

My rationale is that rapalogs in general increase Treg population and at least Everolimus restores youthful immune response to infection.

Its also should be quite compatible with the ketogenic diet (https://www.ncbi.nlm...pubmed/21179166)

 

I also under the impression that low dose rapalogs are quite safe and not really an aggressive intervention. At least in tables for a `failed` study labs results haven't moved much if moved at all http://sci-hub.tw/10...ger.2017.12.026

I would imagine that starting even low dose metformin would shift all those numbers more significantly right away and a lot of people take metformin like its nothing.

Looks like low dose rapalogs are more about slowly shifting ecosystem than an immediate intervention. 



#642 Nate-2004

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Posted 19 June 2018 - 10:06 PM

I am all about immune system regeneration and mitochondrial quality control mostly right now. I think given my consistent exercise over the many years my immune system right now is pretty peak. I don't know if that's why I haven't had so much as a cold in the past 3 years or more or what.



#643 Andey

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Posted 20 June 2018 - 05:42 AM

I am all about immune system regeneration and mitochondrial quality control mostly right now. I think given my consistent exercise over the many years my immune system right now is pretty peak. I don't know if that's why I haven't had so much as a cold in the past 3 years or more or what.

 

  It could be the opposite. In my book, good immunity is to get cold 2-3 times a year with a robust response(high temp, cytokines) and quick resolve. At least for a normal exposure to other people=infection sources. 


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#644 PAMPAGUY

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Posted 20 June 2018 - 12:35 PM

  It could be the opposite. In my book, good immunity is to get cold 2-3 times a year with a robust response(high temp, cytokines) and quick resolve. At least for a normal exposure to other people=infection sources. 

 

No colds for me for over 3 years.  Taking Rapa weekly for 1 1/2 yrs.  My personal opinion is that an excellent immune system is one that is proactive.  In other words, it attacks any bacteria or virus that enters the body and shuts it down before it can cause a cold.


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#645 Nate-2004

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Posted 20 June 2018 - 03:19 PM

  It could be the opposite. In my book, good immunity is to get cold 2-3 times a year with a robust response(high temp, cytokines) and quick resolve. At least for a normal exposure to other people=infection sources. 

 

I'm constantly exposed to germs not just at the gym but with friends, sharing drinks, food, office spaces, kissing sick girlfriends, etc. I don't know if what you're saying is true or not. I just haven't even remotely felt sick at all despite that, but it could also be because of that constant exposure. There have been moments that I thought I might be getting sick but then it's gone in a few hours and was nothing really.  ¯\_(ツ)_/¯

 

Maybe I am getting infected but it's fighting things off quickly.

 

I can't imagine my immune system is compromised at all given the fairly consistent level of exercise over the span of 15 years straight since my 20's. 

 

I wouldn't have such excellent biomarkers coming back from lab work either if it were. 


Edited by Nate-2004, 20 June 2018 - 03:21 PM.

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#646 Decimus

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Posted 22 June 2018 - 06:43 AM

Considering this but probably not worthwhile till I'm 50 no? I'm 44 now.

In the original study noted in this post, the mice were treated for 90 days in middle age and had a maximum lifespan of almost 4 years. That’s a treatment period equivalent of about 6% of their lives. I do not believe that rapamycin affects on lifespan can be explained by the improvement of traditional biomarkers e.g. cholesterol, fat reduction, decreased inflammation etc. In order to get such a massive increase in lifespan over such a short period of time I would assume that there must be some sort of metabolic rewiring going on. Purely speculative, but maybe it changes genetic expression over the long-term of one or more genes responsible for lifespan or perhaps it stresses the body in a similar way as oxidative stress does on cells which ironically then makes the cells more resilient to future stresses. Obviously, this is all conjecture but, the point is that it seems unlikely that such a great increase in lifespan over such a short period of time has much to directly do with any sort of improvements that are yet identifiable and that using rapa in moderation at your age might be beneficial, because the benefits might establish themselves earlier. I’m middle-aged and until data says otherwise I only plan on using rapa for a few more years.
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#647 QuestforLife

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Posted 22 June 2018 - 07:07 AM

I totally agree Decimus. We all want to turn back time, but even with something like rapamycin, with quite extraordinary effects in mice, it can only change things from where we are. And albeit slowly and with great subtly. Having said all that the effects in the long term are quite profound. I've been on it for a year and a half and I look thinner, but I'm still just as strong. My immune system is top notch, but I seem to heal slower. I don't look younger, but the deterioration seems to have halted. These effects are all apparent to a 39 year old.

I'm at the point now where I am going to cycle it off and on, as its such a potent medication that it may interfere with some of my other tests and trials.
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#648 Decimus

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Posted 23 June 2018 - 07:50 AM

Sounds like you’re having a pretty positive response to the rapa. That’s great. I haven’t noticed a whole lot, except interestingly, I suffer from a bit of male pattern hair loss and it has come pretty close to stopping over the course of treatment. I stumbled across an article confirming rapa’s potential use as a hair loss treatment:

http://www.folliclet...approved-drugs/

As far as how many years rapamycin should be run and at what age it would be best to start and stop it, I think the mouse study is still unfortunately the best we have to go on. There’s a study being done on middle age monkeys that will wrap up in a couple more years that should give us our next round of useful info though:

https://www.scienced...60209105352.htm

#649 Jesuisfort

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Posted 25 June 2018 - 01:51 AM

I want to start Rapamycin for intermittent use, but i'm very afraid of immunosuppresant effect

Immune systeme is extremly important,  a weak immune system can lead to cancer... 


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#650 PAMPAGUY

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Posted 25 June 2018 - 10:20 AM

I want to start Rapamycin for intermittent use, but i'm very afraid of immunosuppresant effect

Immune systeme is extremly important,  a weak immune system can lead to cancer... 

 

 

Actually rapa improves your immune system when taken once a week.

 

https://sci-hub.tw/h...anslmed.3009892



#651 smithx

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Posted 25 June 2018 - 10:08 PM

Actually rapa improves your immune system when taken once a week.

 

https://sci-hub.tw/h...anslmed.3009892

 

That study is actually about Everolimus, which is similar but not identical.



#652 PAMPAGUY

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Posted 25 June 2018 - 10:28 PM

You are correct they are not identical. You have to take more of the Everolimus to get the same amount of Tor inhibition. It wears off much faster than Sirolimus because only 1/2 the half-life. It was made for kidney transplant patients who take multiple doses daily. But for the half-life they are identical. Rapa is perfect for once weekly dosing. The above study was sponsored by Novaritis who make Everolimus.

#653 smithx

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Posted 26 June 2018 - 05:25 AM

You are correct they are not identical. You have to take more of the Everolimus to get the same amount of Tor inhibition.

 

Do you have any references for this? It's much better absorbed orally than rapamycin.


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#654 QuestforLife

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Posted 26 June 2018 - 09:19 AM

Many here must have noticed the positive impact rapamycin has on mitochondrial function: higher energy levels and better athletic performance. I have even found that whilst on rapamycin taking NR or even large doses of Nicotinamide and Ribose (as per Turnbuckle's Manipulating Mitochondrial Dynamics Protocol), has no effect.

 

Well now we know why:

 

https://www.ncbi.nlm...pubmed/27720611

 

Mitochondrial functionality is related to cell size, and reaches a peak at an intermediate cell size. Using rapamycin decreases cell size whilst insulin increases it.


Edited by QuestforLife, 26 June 2018 - 09:22 AM.

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#655 resveratrol_guy

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Posted 04 July 2018 - 07:10 PM

If you care about whether or not your rapamycin is real, I just had a mass spec analysis done of one particular brand. Can anyone help me interpret these results? Please post replies over there.


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#656 Ovidus

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Posted 13 August 2018 - 05:40 PM

Hi RAMPAGUY (and Others),

 

I am in my mid 40's and have experimented with 1 mg of Rapamycin a few times. After I take just 1 mg, I wake up the next morning with significantly less pain in places where I had sports injuries in the past. Overall, I feel very fresh and excellent.

 

One time, I tried 1 mg on Monday, 1 on Wednesday and 0.5 on Friday during the same week and felt that was too much. I did get mouth sores and felt a lump in my throat as if I was getting sick (like one poster also described earlier in this thread).

 

But unless I overdo the dose, I am absolutely loving this.

 

Now, I have 2 questions

1- How do we know how much we should take? Is the sores in the mouth the only thing we can go by? Any other criteria we can use? I understand that you talk to a lot of people taking Rapamycin for anti-aging purposes. In your experience, what is the average dose that 45-47 year old guys settle on?

 

2- If I settle on a particular dose -for example 1.5 mg every week- and have no side effects at that dose, is it stil neccesary to take a break occasionally?

 

Thanks a ton



#657 VP.

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Posted 16 August 2018 - 10:43 PM

Hi RAMPAGUY (and Others),

 

I am in my mid 40's and have experimented with 1 mg of Rapamycin a few times. After I take just 1 mg, I wake up the next morning with significantly less pain in places where I had sports injuries in the past. Overall, I feel very fresh and excellent.

 

One time, I tried 1 mg on Monday, 1 on Wednesday and 0.5 on Friday during the same week and felt that was too much. I did get mouth sores and felt a lump in my throat as if I was getting sick (like one poster also described earlier in this thread).

 

But unless I overdo the dose, I am absolutely loving this.

 

Now, I have 2 questions

1- How do we know how much we should take? Is the sores in the mouth the only thing we can go by? Any other criteria we can use? I understand that you talk to a lot of people taking Rapamycin for anti-aging purposes. In your experience, what is the average dose that 45-47 year old guys settle on?

 

2- If I settle on a particular dose -for example 1.5 mg every week- and have no side effects at that dose, is it stil neccesary to take a break occasionally?

 

Thanks a ton

Most believe that pulsed dosing is the way to go. (See Dr. Alan Green) My wife and I are in our late 50's and we take 3 mg once a week. Dr Green is in his mid 70's and takes 6 mg a week.  Rapamycin has a 62 hour half life so if you take it every other day it never completely leaves your body and mTOR c2 starts to get inhibited hence the mouth sores. I also don't recommend grapefruit juice to extend your rapamycin dollars. It too increases half life and can cause mouth sores. 

So the answer to question one is 1-2 mg a week as a guess. Dr. Green will not treat anyone under 50 last I heard. Question number two is unknown. Dr. Green does not take breaks or recommend you take breaks. By default Dr. Green is the worlds leading authority on human anti-aging using rapamycin/metformin but it's still very experimental. 

https://rapamycintherapy.com/


Edited by VP., 16 August 2018 - 10:51 PM.


#658 resveratrol_guy

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Posted 23 August 2018 - 11:45 PM

I've just spent a while on sirolimus, specifically, 3 mg once per week of Dr. Reddy's (Indian stuff from Walmart). I took the first blood test below just before my first dose, and the second just before my 11th. Diet was stable for a month before the experiment, and remained essentially the same throughout. In particular, I've been eating high carbs, moderate fat (mostly olive oil with some coconut meat, eggs, and MCT oil). Protein intake has been kept relatively low, with about 2-4 eggs per day plus the small additional amount in unlimited fruits and vegetables. Grain intake has been negligible, and I probably consumed a can of beans a week.

The first test was remarkable in that it showed my HbA1c at 4.9%, which is at the low end of its range since 2009 (4.8% to 5.5%). Notably, after 3 months of hard keto, it was 4.8% in 3/2015. But after 6 months of low carb (still generally in ketosis, verified by urine test strips, but with a bit more carbs), it had risen to 5.1% by 3/2018. The reason all this is remarkable is because the 4.9% reading was obtained after a month of carbosis, including generous olive oil intake, some avocados, and a bit of MCT oil; I had only restricted protein -- not calories, fat, or carbohydrate. Moreover, I was drinking a lot of juice, probably around a liter per day, on average. I'm not sure what all this means, except that it seems to suggest that while keto is still king for controlling blood sugar, carbosis might be superior to low-carb.

Anyway, on to the sirolimus experiment...

Subjectively, on the first day or two after dosing each week, I would feel bloated and nauseous and get a headache if I ate too much protein. And in general, I've found myself less able to eat so much without feeling full. I didn't notice much of an energy burst that others have reported, although that has now changed since switching to Swiss Garnier (India, sometimes advertised as Biocon) after my second blood test.

As I posted earlier, I had LC/MS tests done which were inconclusive, but were at least consistent with the pills being real. In any event, significant changes do appear to have occurred. I should also note that I started Turnbuckle's Alzheimer's protocol about halfway through the experiment (HEPPS, Longvida, and olive leaf extract, without taurine), but it should have little to no effect on the results, apart from some HDL contribution due to the olive leaf. The only other difference is that I consumed more potatoes and less juice during the experiment, relative to the prior period. Here's what happened, along with an increase in weight from 160 to 163 pounds:

cholesterol total 181 > 194
cholesterol HDL 84 > 69
cholesterol LDL 83 > 110
triglycerides 60 > 67
glucose (fasting) 94 > 81
HbA1c 4.9 > 4.9
vitamin D 25-hydroxy 37 > 46
blood urea nitrogen (BUN) 4 > 7
creatinine 0.97 > 1.02
eGFR nonafrican CKD-EPI 95 > 89
sodium 142 > 140
potassium 3.9 > 4.0
chloride 109 > 105
carbon dioxide 24 > 26
calcium 9.5 > 9.0
protein, total 7.0 > 7.0
albumin 4.7 > 4.5
globulin 2.3 > 2.5
bilirubin, total 0.7 > 0.6
ALP 68 > 72
AST 15 > 19
ALT 17 > 12
WBC 4.0 > 4.0
RBC 4.76 > 5.21
hemoglobin 14.9 > 16.4
hematocrit 42.9 > 47.7
MCV 90.1 > 91.6
MCH 31.3 > 31.5
MCHC 34.7 > 34.4
RDW 14.2 > 12.7
platelets 216 > 201
mean platelet volume 9.7 > 9.9
neutrophils 66.1 > 61.3
lymphs 25.1 > 28.8
monocytes 8.0 > 7.8
eosinophils 0.3 > 1.3
TSH 1.32 > 1.64
testosterone 1109 > 767
free testosterone 103.1 > 53.7
uric acid 6.0 > 5.7
C-reactive protein (CRP) "< 0.2" > "< 0.2"
homocysteine 15.2 > 13.7
IGF1 167 > 157
insulin 4.3 > 6.9
phosphate (as phosphorus) 3.8 > 3.9
LD 146 > 141
GGT 14 > 11
iron 135 > 100
ferritin 53 > 27
DHEA sulphate 115 > 131
estradiol 30 > 28

I've been drinking a lot of grapefruit juice lately, which might account for the slight decline in kidney function. This is particularly disappointing because sirolimus is supposed to rejuvenate the kidneys. Perhaps I need to back off a bit, although I'd prefer not to because it seems to me that this juice is neurologically supportive.

The collapse in testosterone would certainly be consistent with throttling of the growth program. Reduced sex drive reflects this.

The collapse in RDW to its record low since recording started in 2009 is impressive, if puzzling. (It equals the same 12.7 obtained in 10/2009.) It basically means that the distribution of widths of red blood cells is narrower. This sounds like the body is producing more new red cells from the marrow, which would make for a more uniform distribution. (The opposite would be something like leukemia, in which all manner of pathological cells of various sizes might be produced.) Indeed, RBC increased from 4.76 to 5.21. At the same time, iron and ferritin simultaneously dropped, while hemoglobin increased, so if would seem that I'm producing more hemoglobin in order to support those new red cells, which would require the conversion of bioavailable iron. All in all, this points to stem cell release, and might account for the added energy that others experience.

The modest drop in homocysteine is nice to have, and reflects lower inflammation. CRP remains below the threshold of detection despite ingesting terrifying amounts of sugar. Moreso, any drop in IGF1 is welcome, and reflective of putting the breaks on excessive growth. Granted, I don't want to be too hard on either IGF1 or estradiol, both of which being essential to neurogenesis.

But speaking of sugar, insulin has exploded! This is bad by any measure. I'm not sure why it occurred, though. Perhaps it has something to do with the switch in emphasis from fast carbs (juice) to slow carbs (potatoes), so we need insulin hanging around 24/7. This might also be (benign) type 0 diabetes, but my impression is that in that case, we should see elevated glucose with low insulin. BTW fasting was the same in each case, namely between 14 and 16 hours.

The improvement in vitamin D probably has more to do with summer than sirolimus.
 

All in all, I don't really know what to make of these results. Perhaps I ought to get back to more juices and less complex carbs, or perhaps try it with keto.


Edited by resveratrol_guy, 23 August 2018 - 11:50 PM.

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#659 resveratrol_guy

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Posted 24 August 2018 - 07:31 AM

CORRECTION: The LC/MS tests were done on the Swiss Garnier Biotech stuff, not the on Dr. Reddy's that I had been taking throughout the test period. The former is also labelled with "Rocas" and "Emcure Pharmaceuticals" on the package, and as I said it's sometimes sold as a Biocon product, perhaps erroneously.


Edited by resveratrol_guy, 24 August 2018 - 07:35 AM.


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#660 aribadabar

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Posted 25 August 2018 - 01:15 AM

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.

 

iron 135 > 100
ferritin 53 > 27

At the same time, iron and ferritin simultaneously dropped, while hemoglobin increased, so if would seem that I'm producing more hemoglobin in order to support those new red cells, which would require the conversion of bioavailable iron.

 


Edited by aribadabar, 25 August 2018 - 01:17 AM.






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