Len5742 - My Rapamycin Diary

[anon16510610]

I ran across an article where Dr. Green described the improvements that rapamycin wrought. That’s what brought me here. Would like to induce something similar.

I hope to use this entry to track my results, quantitative and subjective.

I will post some quantitative data as soon as I get test results from todays visit to Labcorp. I didn’t take a ‘before’ snapshot, but I have enough Kaiser history such that I hope I can construct something useful.

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Perfil

Caucasian male

age - 70y 5m

weight - 125 lbs BMI - 18

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Fitness

Completed three 2000+ mile hikes at ages 59-61. Last long hike in 2019, six hundred miles.
Could still get over 5000 meter passes in Nepal, as of 2021.

Weekly exercise includes: 2-3 150 minute walks carrying a 27 pound backpack.
Once a week 5 hour hike which includes some 30%+ grades.
3-4 20 minute sessions of general stretching, sit-ups and push-ups. Very limited weight lifting.

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Physical issues

Gelatinous transformation of bone marrow - as of 2003 biopsy.

Various out-of-bounds blood counts, noted since the bone marrow determination. Out of bounds, but stable.

-No symptoms associated with the above, accidentally uncovered when I injured a foot, and the usual blood tests were administered.

Osteoporosis

Poor dental health.

Osteoarthritis in hands and feet. Pain is minor, but let’s skip shaking hands.

DVTs in both legs. Taking Pradaxa.

Tinnitus

In 2016, I decided to try lifting weights after not doing so for four years. Induced neck and shoulder pains that can’t be eliminated. Issue involves muscles, not bones. I can still carry a backpack, but it’s a lot more painful.

Generalized aches and pains and tiredness that one usually associates with getting old.

…that’s enough.

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Supplement regimen

Pradaxa, glucosamine/chondroitin, creatine, calcium, vit D, multivitamin, omeprazole (stopped for now) melatonin for sleep, verisol collagen, hyuralonic acid.

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Rapamycin Objectives

Easily-noticed decrease or elimination of general aches and pains.

Overall feeling of greater energy.

Improvement in gum disease, noted by dentist without prompting.

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Dosage plan

Started January 6, 2023 2mg Biocon Rapacan. Additional weekly doses - 3, 4, 5, 7, 10mg (today, Feb 10). Plan to continue at 10mg or greater. Not adding any boosters.

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Benefits so far: None noted.

Side effects

A ridge on the inside of my cheek after the first dose. Receded after a few days.
Skin blemishes are ongoing, on scalp, face, elsewhere. Very annoying.
Some itching, seems to be reduced now, but still there.

[blsm]

Very cool, we started about the same time.

[RapAdmin]

@anon16510610

In 2016, I decided to try lifting weights after not doing so for four years. Induced neck and shoulder pains that can’t be eliminated. Issue involves mu

Len, Welcome to the site, and thanks for posting your introductory message. I’m a hiker also, but have done nothing compared to the mileage you’ve been racking up the past decade! Great to see the amazing efforts and milage… I assume you’ve done the PCT (Pacific Crest Trail) … sounds like the entire route, given the mileage), and what other hikes? I’m envious. Nepal is also a fantastic area to hike in - I’ve trekked in the Annapurna sanctuary area, but would like to get back and do more.

Regarding your shoulder pains after weight lifting. I had something similar that went on for two years… I rested, thinking that I had just strained it and it needed to recover, but it didn’t change over two years. Then I spoke to a friend who is a physical therapist, she gave me some simple exercises to do at home, and it was cured in a few weeks of exercises. Obviously, your mileage may vary, but I highly recommend at least trying a good physiotherapist if you haven’t already.

I think there is a reasonable chance that rapamycin will help with many of the aches and pains you mentioned, and get your energy to the level where those 2,000 mile years of hiking are something you can again feel good doing!

If you haven’t already, I recommend you review the “benefits” sections (and side effects), in our FAQ: Rapamycin Frequently Asked Questions (FAQ)

[anon16510610]

Thanks, hopefully I can contribute some useful data to rapa investigation, and see some improvement in my many defects.

Re: Shoulder/neck pain - I consulted with Kaiser - ‘Oh, your problem is obvious…’ I had ‘forward head syndrome’. That, plus the curvature of my spine at the top, means that the muscles are under constant stress, so I’m told. PT gave me a bunch of stretching exercises, and after a couple weeks, voila, I was visibly more erect, head and neck-wise. The result was some reduction in pain but far too much remained. I continued on for a few months with recommended exercises, but pain only got worse. Acupuncture accomplished nothing. Six years later, no improvement.

Dysfunctional bone marrow and osteoporosis notwithstanding, my spine elements (per a MRI) are actually in quite good shape.

Re hiking: I retired from my IT job at age 55. No idea what I was going to do. ‘Well, I like to walk…’ Learned of the Appalachian Trail. Decided to make hiking that a retirement goal. Just one problem. Had never done any hiking/backpacking. Never slept outside. A steep learning curve ensued. In the process, found out about the PCT, which starts just east of here (San Diego), so revised my goal.

My first multiday hike, in 2007, was on the John Muir Trail. Managed to complete about 2/3, had to exit. Despite contracting pneumonia and inducing second degree burns on the back of my hands, I was hooked.

I tried to hike the PCT in 2008 and 2009, made to Oregon both times, but stopped for…reasons. Finally made it end-to-end in 2012. Completed the AT in 2011, 2/3 Continental Divide in 2013. Completed a few other US trails over the years. Also, treks in a few other countries. Would that I had got started on this 20-30 years sooner.

All it takes is time and money, lol. Some people have a life, that can get in the way, so I’m told. One key to facilitating long hikes is having someone at home to send you supplies. My poor sister, who has to stay home and work for a living, has filled that role. Many, many, thanks to her.

Photos: Len - len5742

[Sirt6]

Short question, why aren’t you taking K2 to your calcium and D3? Or do you eat a lot of grape seed oil or Nattō?
I try to always combine D&K.

[anon16510610]

@Sirt6

why

Lack of knowledge. I don’t ingest those other things you mentioned. I’m not a nutrition enthusiast. I should look into K2.

Post osteoporosis diagnosis, calcium/vit d supplementation, plus alendronate (now stopped) were recommendations from the Kaiser ‘Healthy Bones’ department. I do make an effort get some calcium from foods rather than pills.

[RapAdmin]

@anon16510610

Photos: Len - len5742

Len - Loved the photos! Tour du Mount Blanc is on my bucket list. As are many of your hikes. I hope we can keep these types of activities up for another 50 years with all these longevity medicines and treatments coming online!

[Phil_Van_Treuren]

@anon16510610

Completed three 2000+ mile hikes at ages 59-61. Last long hike in 2019, six hundred miles.
Could still get over 5000 meter passes in Nepal, as of 2021.

This is really impressive! And your current exercise schedule as well.

[blsm]

@anon16510610, thank you for sharing your pictures! It’s really cool that there’s an option to buy prints. I found one I’d love to purchase as a gift for my Godmother.

[John_Hemming]

This paper i think gives a solid mechanistic cause for osteoporosis

https://www.nature.com/articles/s43587-021-00105-8

It started me on my theory of aging

Its the long genes that stop working

[anon16510610]

Feb. 10, 2023 Marek results posted below, plus Levine calculation. I fudged the creatinine number from 1.6 to 1.3 to compensate somewhat for creatine supplementation. (I have stopped creatine for now.) Which one do people quote, the pheno or DNAm age?

Comment on the 40ng/ml rapa level. I took 10mg rapa with a Luna Bar at about 9am. (I had eaten some rice about an hour before.) I had an lab appointment at 10:45am, and the document says blood drawn at precisely 11am, so two hours post-ingestion. Maybe Luna Bars are the new EVOOGFJ? Is there any consensus on what level to shoot for here?

The flagged CBC values, and the other CBC values overall, are consistent with history. Though maybe the RDW coming in within range might be new, I’ll have to check. I will add some historical plots from Kaiser data later.

[RapAdmin]

Wow - that is a surprisingly high blood sirolimus level. you must be a good responder. We really don’t have a good idea on the Tmax level for sirolimus we want to target (or really, the AUC, as that is likely the key thing).

I’ved posted this before… perhaps a guide generally.

On the Tmax level, in the NIA ITP mouse studies, generally the higher the dose, the better the lifespan increase. (but remember, the mice in the ITP studies live in pathogen-free environments so don’t have to worry much about getting infections… we live in a very different world).

In one study ( of the 45+ studies of rapamycin in mice) they did finally find an upper dose of rapamycin that no longer increased lifespan in those female mice. It was an extremely high dose though.

I should note that in mice there is a significant dose / response difference between male mice and female mice. This difference is not seen in humans.

Most of people currently using rapamycin seem to be (in mouse equivalent dosing) in the low levels tested (note: mice were dosed rapamycin in their food, daily, so that is another difference - vs. us using rapamycin dosed once weekly or so).

Here are the National Institutes on Aging Results from their rapamycin studies (these are the best rapamycin studies done on rapamycin. Note, the blood/sirolimus levels are perhaps more constantly high in mice because the rapamycin is mixed in with the food so they get it every time they eat):

Sirolimus Dose	mg/kg/day Dose	Blood/Sirolimus Level	Male Median LS Increase	Female Median LS Increase
4.7ppm	∼2.24	3 to 4 ng/mL	3%	16%
14ppm	~6.67	9-16 ng/mL	13%	21%
42ppm	~20	23-80 ng/mL	23%	26%

Here (below) are the results from all the higher dose studies I could find. Note the highest doses are from the “Transient rapamycin treatment” trial that Alessandro Bitto did at the University of washington with Kaeberlein, where they only dosed the mice for 3 months (so while the lifespan was increased by about 15% total, you can’t directly compare the longevity data to a dosing schedule where the mouse got the rapamycin for the later 2/3rds of their lives):

Sirolimus Dose	Mouse mg/kg/day Dose	Mouse: Blood/Sirolimus Level	Human mg/kg/day Dose	Dose for 60kg Human	Daily Dose adjusted for longer half-life (/4)
4.7ppm	∼2.24	3 to 4 ng/mL	0.182 mg/kg	10.92 mg	2.73 mg
14ppm	~6.67	9-16 ng/mL	0.542 mg/kg	32.54 mg	8.135 mg
42ppm	~20	23-80 ng/mL	1.626 mg/kg	97.56 mg	24.39 mg
126ppm	~60		4.878 mg/kg	292.68 mg	73.17 mg
378ppm	~180	45 to 1800 ng/mL	14.634 mg/kg	878.04 mg	218 mg

Based on the FDA animal to human dosing conversion guide here.

Note: ½ life for sirolimus in mice is approx. 15 hours, vs. approx. 62 hours in humans. So, mice metabolize sirolimus approximately 4 times faster than humans.

[anon16510610]

Some historical context:

Selected Historical Plots.pdf (242.6 KB)

[anon16510610]

3/18/23

Osteoarthritis

Some comments about my experience with rapa and the progression of my arthritis. TLDR; Not helping so far. Perhaps even aggravating, but could be confounded by the concurrent initiation of weight lifting.

Feet

In 2006, I broke a small bone in my left foot. A foot xray showed some arthritis.

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DEGENERATIVE ARTHRITIS: Degenerative arthritis is identified. There is no bone destruction or fracture recognized. There is no significant additional pathology recognized. There is no radiopaque foreign body seen. SUMMARY: Degenerative arthritis.

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Disturbing to read. But to date, this has been virtually pain-free. Arthritis also identified in the other foot, has not been a problem.

Hands

Mid-2020, went for a hike, noticed that after several hours of gripping a trekking pole my hands were aching in a way they hadn’t before. Xrays confirmed osteoarthritis.

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IMPRESSION:
No acute fracture is identified. The alignment is normal. Moderate
osteoarthritis bilateral, right greater than left, thumb
carpometacarpal joints. Bilateral scattered mild osteoarthritis. No
significant soft tissue abnormality is identified.

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Up until recently, my experience with my hands that the left virtually never bothers me, while the right thumb and forefinger are prone to some ‘excitement’ if stressed in the wrong way.

Right elbow

Starting several months or a year ago, my right elbow aches on occasion, while stressed. No confirmatory xrays, but I assume it’s evidence of more arthritis.

Weight Lifting

Six years ago, I tried to re-initiate weight-lifting after not having done so for four years. I strained some muscles in my neck, shoulders and back. Tried some PT, but didn’t solve the problem. I tried to start weights again a couple of times, but it made my back hurt such that I couldn’t carry a backpack.

I gave weights one more try shortly after starting rapa in early January. This time, and until now, have not induced the pain that made it prohibitive before. ‘Weights’ meaning squats 3x7 reps, and forearm curls the same. With a very minimal amount of weight.

I’m not giving rapa credit for making this possible (yet), as everything that aches, still aches. Just not debilitating.

Increased frequency of pain in hands and right elbow

Also since January, my hands and right elbow are bothering me more, at an increasing rate. The ‘ouchie!’ moments are increasing in frequency and intensity. Oddly enough, the pain is not experienced while lifting weights. (Nor while doing three sets of pushups.) It’s random tasks throughout the day that set it off.

An internet search of ‘weightlifting and arthritis’ seems to turn up only positive articles. Not much on rapamycin.news for ‘arthritis’. Highest number of references seem to be from one individual…

Will be mostly traveling from the end March to mid-May, so not lifting any weights. But will continue taking rapa. Will see how I feel in a couple of months.

[anon16510610]

Nothing interesting here wrt rapamycin. Just uploading for comparison after I scan a year from now.

If you are in the San Diego area, you can get the the following DXA body composition and bone scans done for FREE at UCSD EPARC. (Free Scans – School of Bone Densitometry – DXA Training, UC San Diego)

I paid for mine ($250 for both, or $150 for one) because I couldn’t get my availability to align with their free windows.

UCSD Body Composition_DXA_LGlassner_Apr 2023.pdf (970.2 KB)
UCSD DXA Report (Bone)_LGlassner_Apr 2023.pdf (1.0 MB)

Adding the following for historical reference:

DXA History at Kaiser

03/07/17
DXA Key Findings:
Lowest T_Score: -3.2 Region: AP Spine L1_L4
Lowest Z_Score: -3.1 Region: AP Spine L1_L4

BMD CHANGE from DXA on 09/16/15:
3.0% AP Spine L1_L4
-1.7% Femur NECK Left
1.3% Femur TOTAL HIP Left
-2.4% Femur NECK Right
4.5% Femur TOTAL HIP Right

09/16/15
DXA Key Findings:
Lowest T_Score: -3.7 Region: AP Spine L1_L4
Lowest Z_Score: -2.5 Region: AP Spine L1_L4

BMD CHANGE from DXA on 07/18/14:
-2.0% AP Spine L1_L4
3.3% Femur NECK Left
-1.6% Femur TOTAL HIP Left
0.9% Femur NECK Right
0.3% Femur TOTAL HIP Right

BONE MINERAL DENSITY TESTING
L1 T-score -3.5, Z-score -2.3
L2 T-score -3.7, Z-score -2.5
L3 T-score -3.7, Z-score -2.5
L4 T-score -3.9, Z-score -2.7
L1-L4 T-score -3.7 , Z-score -2.5, BMD 0.778 g/cm2
L Femur lowest T-score -2.7, Z-score -1.7, BMD 0.718 g/cm2 total
R Femur lowest T-score -2.7, Z-score -1.7 , BMD 0.710 g/cm2 total

07/18/2014
Hip and Spine Key Findings:

Lowest T-score: -3.6
Lowest Z-score: -2.4

[anon16510610]

Test results after 5.5 months of rapa. See below.

Comments welcome. My comments:

Positives:

• This is the first time in the last 20+ years of tests that all the basic blood counts have fallen within standard range at the same time. First time ever for RBC and MCV not coloring outside the lines.

Physically, do I feel any better as a result? No. Mentally? A bit.

My understanding of RDW falling below reference range just means the cells are more uniform in size than usual, but that only matters in the context of problems elsewhere.

• Fasting glucose at 89. Doesn’t seem to indicate a problem with glucose levels, rapa usage notwithstanding, correct?

• First time I’ve had a Cystatin-C test. eGFR of 87, which is considerably better then the creatinine-based eGFR (not in these results) of 54 I get from Kaiser. (Kaiser refused to do a Cystatin-C test)

Less Positive:

• Elevated lipids. Not surprising, I guess? And Apo-B going from 81 to 99. All of a piece? But then the LDL/HDL ratio is 1.8, which has ‘1/2 the risk’, per the report. (Of what, CVD?)

• A1c just below getting flagged as ‘pre-diabetic’. Previous Kaiser readings:
  

labcorp results 6-20-23.pdf (647.2 KB)

[anon16510610]

Just to add a little more ‘checkpoint’ info:.

The zits and itching from weekly dosing (of 10mg) more or less disappeared a while ago. No ‘euphoric fatigue’ from ingestion, more like caffiene-like angst for a few hours.

My fingernails grow a lot slower lately. This, I welcome. Also, definitely feel colder than I used to.

Ok, adding one more observation: It might be the case that I can eat a bit more than I would expect, and not gain weight. Not particularly important, as I weigh around 120lbs.

[John_Hemming]

I am not sure I would welcome slower growth of nails as that would be a general stem cell reproduction issue.

That is another reason I think every 2 weeks is 2 frequent.

[anon16510610]

The rate my fingernail growth has accelerated considerably in the last few years. What is that all about? That’s why I said I welcome the slow-down.

[John_Hemming]

Common nail changes and disorders in older people: Diagnosis and management

“Nail plate growth rates of fingernails and toenails normally average 3.0 and 1.0 mm/mo, respectively. With advancing age, starting at the age of 25 years, this rate tends to decrease by approximately 0.5% per year.”