" Fifteen patients with PTEN-deficient tumors, who also met all other eligibility criteria, were enrolled at the time of tumor recurrence and received neoadjuvant oral daily rapamycin (2 mg, 5 mg, or 10 mg/d) for approximately 1 wk (median: 6 d, mean: 7.5 d) prior to salvage surgical resection (S2). After recovery from surgery, patients resumed daily rapamycin treatment at the neoadjuvant dose until clinical and/or radiographic evidence for tumor progression was found."
“The last preoperative dose of rapamycin was given on the day of craniotomy and peripheral blood was collected within 24 h of surgery.”
So even patients taking only 2mg/day, this can generate significant blood and tumour concentration of Rapamycin, and most importantly, brain TISSUE activity of mTOR as measured by S6 phosphorylation.
"Inhibition of Tumor Cell Proliferation Is Correlated with Magnitude of mTOR Inhibition"
If Rapamycin passes through the BBB passively in a concentration dependent manner, without a transporter complicating interpretation, might be interesting to do some pharmacokinetics modelling of the AUC of our single weekly dosing model vs a lower daily dosing model, try to extrapolate to this study.
Has anyone gotten any further insight into Dr B/Dr Green and their higher Cmax/BBB comments?
Yes, you are right here. I interviewed Allesandro Bitto of the university of Washington lab and he said that rapamycin easily passes the blood brain barrier (in mice)… Will post that when i get to my computer…
But the evidence seems to suggest that higher doses are not needed to penetrate the BBB.
I perused several sites about this (BBB) and looks like there is some evidence that in humans it does penetrate the BBB.
Also the figure for molecule size and passage across human BBB …rapa is about 30-50% larger than the quoted “passage” value in literature… are not absolute as the figures are estimated and passage also depends on other things.
Last, if 10mg does not pass, 20 mg is also unlikely to make it through…or 40 for that matter.
I have questioned why Green and others …after having great results on 6-8 mg went to 20mg. The BBB passage is often given as the primary reason.
Have you recently done a complete iron panel and/or ferritin? Might give you further insight into your reserve. Do you know if you have any wonky iron genes?
Iron Deficiency: serum ferritin less than 12 µgr/dl and transferin saturation percentage less than 15.
Iron deficiency anemia: serum ferritin less than 12 µgr/dl, transferin saturation percentage less than 15, and Hb less than 14 mg/dl.
I haven’t done a full iron panel for about a year, but last checked, saturation was low, 21%
On a recent panel (August '21), my ferritin, 2 weeks after last donation, was 12. It’s been hovering 20 or less for the last 18 months.
I am a high daily exerciser, really don’t feel any classic anemia effects. My CBC’s remain completely in normal range, although low end.
Trending low since starting rapamycin, but I also have been eating less due to loss of appetite and have lost ~8 lbs since starting rapamycin. I now have to force myself to eat more to maintain my body weight. My current BMI is 22, which is the BMI I was aiming for.
If I Iook at your body type in 2016, only 6 years ago, or age 59 (and I don’t know your body type, diet, exercise regime) for the 1st 59 years or if this persisted to more recently, this is classic metabolic type syndrome and risk for cardiovascular disease.
I would suggest you look “under the hood” at the health of your heart to make sure CVD is also being addressed. Weight, muscle size, the mirror…all readily visible markers of your improving health trajectory, but tells you nothing about your heart status.
Your 1st 59 years may have created an atherogenic risk, that you cannot see unless you check your heart itself inside, and do not be assuaged by current blood markers (lipid panel) and think “everything is ok”.
You might consider a coronary calcium scan of your heart, looks at plaque deposits. This will give you a baseline of your risk stratification. It’s not expensive, can settle things.
Not a doctor, only suggesting that if you’re “that” serious about your health and all cause mortality, check out your heart!
Really appreciate several of your follow-up replies. On grapefruitl morning of and a few hours before rapa intake… gonna do this on Monday.
Even exercise during rapa use.
I typically exercise the day of rapa… and read recovering muscles are activated for up to 24 hours after a work out. So a little less concerned on this now.
I do a brisk walk of my small town… 3 miles in about 40 minutes. On non- work out days… and walk a lot a work… so getting cardio… but the damage of 59 years can’t be ignored.
I see my physician next Friday…he trusted and supported me to go on the rapa journey. Great timing to order the heart calcium plaque scan. The medical university has great insurance… Cigna covers everything… 3 month check-ups, fullblood work…includes my rapa which was almost $700 per month at first… now about $450.
Annual cost to be checked and healthy is about $33,000… my out of pocket about $1,100.
So will add this test and see what it says.
When I started rapa… I really felt it hit my heart hard the first few weeks… can only describe it as my heart felt heavy and full. The dimples in my arm blood veins opened and vanished over the first years… looked like a bent garden hose… then all opened and constant pulse became visible… so hoping my bad eating habits harden arteries have cleaned up. This test should tell. Thanks bud! Gym time - ugh!
Apparently, my total cholesterol peaked during my first round, but not my second round.
I keep my cholesterol under control through diet and exercise. My main food and supplements for cholesterol control are oatmeal, Omega 3s, and olive oil.
My latest results may be somewhat skewed because I was not eating much or my usual diet. About two weeks before my scheduled test, I contracted the flu/covid/cold? I don’t know which, but I just stayed home and didn’t see a doctor because I didn’t feel too badly and didn’t have a fever. It was mostly bronchial coffing and hacking and continuous sinus drainage. I haven’t ever had any allergy attacks like this, but who knows. Then I got a tooth infection. Maybe related to high dose rapamycin and was put on anti-biotics by my dentist a week before my blood tests.
“It is important to recognize that the current evidence is not enough to conclude that the relationship between resistance training and survival has a U-shape curve. People performing a high volume of resistance training may be more likely to use anabolic–androgenic steroids or supplements with substances that could adversely affect their health”
Combine resistance with aerobic (FAR more compelling longevity enhancement with VO2 expansion), and what are we talking about, +/- 15% extension in lifespan? What are we expecting with current TOR1/TOR2 suppressing intermittent Rapamycin?
My latest blood tests after two months on higher doses (10 to 20mg) of rapamycin entered into the epigenetic age calculator.
Basically no difference than two months after I started on 5mg doses.
What is not shown here is the increase of triglycerides from 121 to 151mg/dL and an increase of HDL from 49 to 60mg/dL. Though total cholesterol is down from 186 to 157mg/dL.
Rapamycin may also be driving my PSA lower from an already low of 0.9ng/mL to 0.8ng/ml.
If anyone is interested in any other parameters from my latest test I will supply them.
Six months into rapamycin. While I can’t say it helps with muscle growth, it’s definitely not interfering with it either. Currently taking 10mg with GFJ every second week.
Age 50, no TRT, testosterone or other hormones. I do take tongkat ali and fadogia agrestis for endogenous T and decreasing SBGH.
That’s not a Rapamycin six pack. That’s serious resistance exercise/sweat. Kudos.
Do you do any aerobic?
I’ve seen no blunting of muscle building on weekly Rapamycin. The higher the volume of exercise and load max, the bigger the muscles. 18 months on Rapamycin (various dosing regiments), daily high exercise.
The whole mTOR blunts muscle, don’t exercise on dosing days…I don’t subscribe. Sure, you can find studies on very specific muscle group biopsies post Rapamycin dosage in humans, showing mTOR blunting. This narrow physiological experiment gets translated into mainstream dogma that “you cannot build muscle on Rapamycin”
The mirror does not lie.
There are mTOR independent and Rapamycin mTOR insensitive pathways to muscle protein synthesis. This I have confirmed in many studies and independently confirmed with various researchers in the field.
Furthermore, Dr B says:
Amino acids don’t build muscles, exercise does.
Rapmycin potentiates strength.
Exercising everyday whilst taking Rapamycin is “optimal”.
Exercising when it is more difficult, be that on Rapa, Metformin or blood flow restriction, is going to make you stronger when that extra difficulty is removed.
