#26

Ok I understand. Thanks for the confirmation, there are often misunderstandings on forums

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#27

Yes - I also believe that this is the case. I worked on a gene therapy startup company about 15 years ago and one of our areas of focus was looking at intra-muscular insertion of extra copies of the IGF-1 gene as a way to counter sarcopenia. If you avoid sarcopenia the thinking is you greatly reduce the risk of falls and broken hips.

The statistics are really sad for people who break a hip at an advanced age; 50% of people who break a hip (over the age 60) die within 2 years. It marks a fundamental change in their life trajectory. You really don’t ever want to break a hip.

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#28

Had my DEXA score - normal. I have a 1% chance of breaking a hip in a fall based on my numbers.

Now taking a daily calcium supplement 1000 mg to maintain my good bone density. Despite all the milk I drink - you get about 90mg of calcium. WIth my weight resistance exercise every other day… muscles take calcium… I definitely need to increase my calcium intake.

I was told by the physician you can’t reverse any bone loss from aging, but with supplements you keep what you have - prevent progression. Been thinking I should let those men on here over 60 - need to think about adding calcium to their supplements - women already get ample warning about needing more calcium. See my DEXA for bones and body composition. With rapamycin - no visceral fat. Normal range.
DEXA and Body Compostion Scan.pdf (1.5 MB)

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#29

Your doc said bone density cannot improve? I am pretty sure that bone mass will increase in all but the oldest individuals as an adaptation to stress. Hard work is required. Calcium, vitamin d, vitamin k, and resistance training are necessary and it takes time. A sarm like lgd4033 would help but has associated risks. I’ll bet this guy’s dexa score improved:

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#30

You require more than “daily calcium” to increase bone density.

Review the article and paper on mega K2 – 45000 mcg {yes, 45000mcg] of MK4.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866409/

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#31

Really it’s irrelevant what comes first, the fracture or fall. The solution is still the same: to prevent osteosarcopenia, which high impact exercise and protein have been shown to do.

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#33
  • Human trials have shown that daily intake of 45 mg of vitamin K2 (MK-4) maintains or increases bone density and cuts the risk of fractures.

Thanks for this… something to go with the calcium. I have zero calcium deposits or plaque in my coronary calcium scan… so will stick with the calcium for now.

#34

Member “rivasp12” is the one who pointed this out earlier last year.

I recall he stated he had been taking the 45000mcg dose for some time and that only 1 company{Life Extension] sells in that dose size in one capsule, sold as Mega Vitamin K2.

Got me taking for a while, not recently.

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#35

Actually running increases AMPK which reduces Mtor. This maybe one of the reasons why people who have been life long runners tend to be biologically younger in certain aspects. Weight training can do the same but it would have to be fast to create oxygen deficit. During running it is true at some stage it does increase Mtor but overall it is beneficial concerning Mtor. In fact exercise is the best overall strategy for longevity

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#36

Hello Mac, I just noticed this comment of yours. Does this have something to do with your plant based diet? I also have a plant based diet, and when I had it checked my ferritin was very low. Since that time, I have been adding a small iron supplement to my daily stack.

#37

FWIW: I am on a relatively low carb high protein diet and eat a fair amount of red meat.
Since taking rapamycin for 1+ yrs all indicators of iron levels have dropped since taking rapamycin. My doctor recommended stopping rapamycin for a while and taking an iron supplement, which I am doing. I believe rapamycin tends to produce anemia.

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#38

Thanks for the quick reply. I regularly check my iron levels so that’s something for me to consider when I do my next blood check as I started rapamycin about a month ago.

#39

Dennis Mangan, the Dumping Iron author, would probably argue that it is good to be a bit anemic. Perhaps part of the longevity benefit from Rapamycin comes from reducing iron levels.

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#40

But does that not make you tired all of the day? Something was, and to some extent still does, make me tired (maybe it’s old age), but I feel a bit less tired lately after taking iron supplements.

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#41

No, this is majority related to my 5+ yrs of 8 week regular blood donations to dump iron, and the full on crossover/decline due to the recent high dose rapamycin protocol (started July '22); nothing to do with diet. I eat a plant fat based, low animal protein based keto diet, no issues with iron intake. The iron dumping (200-250mg/donation) is one of my major lifestyle intervention hacks for cardiovascular, neurodegenerative, cancer, and anti-aging benefits (PM if you want some paper links). The goal was to skirt just above “classic anemic markers” balancing with exercise output/recovery and how I generally felt (fatigue, dizziness, etc).

We know from many clinical studies that rapamycin fundamentally and very significantly disrupts iron regulation, and anemia is a well known and very common side effect (for therapeutic dosing, NOT low, intermittent dosing that people take here).

Here is a good reference on high dose therapeutic rapamycin (what I am doing) and iron dysregulation:

https://sci-hub.se/https://doi.org/10.1093/ndt/gfp674

What’s also interesting in this very good rapamycin/iron study is that oral iron intake did not alleviate Hb and MCV during therapeutic rapamycin…only IV iron was able to reverse (see Table 5)

So my already borderline anemic markers were flipped to the full on “classic iron deficient anemia” after starting my high dose rapamycin protocol, but the interesting observation is lack of symptoms (to date) and able to continue my high daily exercising regiment (45 mins resistance, 3-5km Zone 2-3 cardio), without any impact or tiredness normally associated with clinical anemia. I am not 100% sure what n=1 dynamic is at play. It could be adaptation from the long term iron reduction (what my doc thinks), much higher genetic cellular iron stores than markers indicate (what I also think at play; I am homozyous H63D, so tend to store iron: Individuals homozygous for the H63D mutation have significantly elevated iron indexes - PubMed), high dose Vitamin C holding onto iron, other… But it’s still early days from a therapeutic dosing/iron dsyregulation dynamic. Thus, with markers screaming 911, I stopped donating blood (July '22 was last) when my ferritin reached 13 and saturation 9% (more concerning), as possible warning indicators for iron stores on this protocol as a precaution. If you read the paper link above (reminder, this is THERAPEUTIC dosing), iron dysregulation was ongoing during the 24 month period of this high dose rapamycin cohort (See Table 2: continuous dropping MCV, ferritin, and continuous increasing % microcytosis): I am just passing through 6 months. As a further confirmation of the dynamics findings in the above study, my MCV just hit lower lab level, and my RDW just crossed over into high, but my ferritin and transferrin bounced up some (Nov '22 labs). Clearly, my body systems are still remodelling, and I will continue tracking very closely going forward.

If you’re on a plant based diet, then you likely know you might be lacking in iron and other nutrients that are found in animal protein sources. Ferritin is a VERY poor measure of cellular iron stores, arguably useless unless perhaps at extremes as a broad indicator. I would do a full iron panel besides ferritin, and look at iron saturation whilst you take rapamycin to monitor more closely, along with full CBC. Also, if you have genomic data, look at your iron genes (although it appears you don’t have storage issues).

https://sci-hub.se/10.1146/annurev.med.50.1.87

https://sci-hub.se/https://doi.org/10.1007/s10620-006-3210-3

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#42

As a life long runner who has been taking rapamycin for over 3 months now, I can tell that dosage needs to be slightly different for me. I’m not certain if that’s the case for all aerobic exercising athletes or not.
Gradually building up to 5mg with EVOO I’ve noticed some side effects that I don’t particularly like. I noticed that at 2 or 3mg with EVOO and regularly running the every day benefits seemed more in line with what I was after. I’m currently about to do a 3 week washout period and then amp backup, maybe stop at 3mg and see if there are any side effects.

Also, I think it’s important to understand that being anemic and doing regular exercise is exhausting and almost impossible. I understand that being slightly anemic is better for longevity, but I feel like this is in the non aerobic exercising population. If you are regularly doing long bouts of aerobic exercise, you are taxing your red blood cells and mitochondria in a similar manner (probably slightly different) as taking rapamycin.
I think it’s healthier to do aerobic exercise if you want longevity. I feel like rapamycin can play an important role in rolling back the clock and making aerobic exercise more fun. I’m watching my iron levels very closely because if I become anemic it’s likely due to mixing rapamycin and lots of aerobic exercise.

Seems like walking on a tight rope trying to mix the two together, but one that could pay off if carefully figured out.

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Endurance Athletes Using Rapamycin?
#43

“serum ferritin levels are generally accepted as reliable single indicators of the presence of iron deficiency” From the article you cite.
Just sayin.

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#44

Thanks for this suggestion. Is it also the case that exercise can cause ferretin levels to be low. My usual routine involved a 10 or more km walk and being a vegan (before), I had very little of the foods that might provide iron.

My ferritin was down to 11 and a month after I started taking a small dose of supplement (before starting Rapamycin), it was up to 20. I will certainly pay attention to the iron levels and look into what additional iron tests I can get from now on.

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#45

Are you under the care of a doctor? I ask because a ferritin of 11 would have most docs go apoplectic. My FMD doc told me his red line minimum ferritin level was 80 (no other marker/insight/factors)…I blew past that years ago. Where I am, for men 50-59 yo, the lab range for low-high ferritin is 18-543, respectively.

99% of general practitioners have almost no knowledge of the complexity or iron regulation. They utilize standard playbook (med school, lab cutoffs), and as soon as you trigger, they put you on iron supplementation. I’ve seen that twice in my own immediate family without any deeper analysis of underlying.

Some definitions that factor more than ferritin:

Iron Deficiency: serum ferritin less than 12 µgr/dl AND transferrin, saturation percentage less than 15.

Iron deficiency anemia: serum ferritin less than 12 µgr/dl AND transferrin saturation percentage less 15, AND Hb less than 14 mg/dl.

Of course, these are just a next layer of iron panel markers (very few people do a full iron panel), and one must consider the entire person overall characteristics. The takeaway is rapamycin will dysregulate iron homeostasis (negatively), so one should be far more vigilant with iron markers/symptoms, especially if food type iron intake is low. And MOST especially if you are trying to proactively lower iron.

I am not a medical professional, this is not medical advice.

image

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#46

Back to the original topic of this thread, here is a reference from the famous Blagosklonny paper

“Physical exercise may be most beneficial starting immediately after rapamycin use, to take advantage of rapamycin-induced lipolysis as a fuel for the muscles.“

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