Rapamycin and Acarbose effect on bone health

#1

I am curious if anyone has experienced bone health issues that might be related to rapa or acarbose.

I am a male in my late forties and was diagnosed two years ago with mild osteopenia. My doctor advised me to supplement my vegan diet with supplemental calcium (1g/day) and continue taking vitamin D and K2 as well as doing running and resistance training - I have been doing all of that to this day. This was about the same time when I started using weekly rapa (6mg) and daily acarbose (100mg).

I did recently a new DXA, and to my shock, my bone mineral density had lowered considerably. Since finding out, I have seen an endocrinologist to figure out what is going. My health markers are great overall, except that my SHBG is significantly elevated, and as a result my free T is on the low side (although still within the reference range). I am reasonably lean, currently my fat percentage is about 12%, but it has been between 7 to 9% for most of the past two years.

I havenā€™t yet discussed the rapa and acarbose use with the endocrinologist, but I did ChatGpt deep research, and it suggests that there could be a connection. I realize that ChatGPT answers should be taken with a grain of salt, and that is precisely the reason I am trying to gather more points of view on this topic.

Here is the synthesis from ChatGPT deep research (references removed for readability):
Bringing the above together, the patientā€™s apparent osteoporosis/osteopenia is probably multifactorial. The most plausible physiological explanation is the convergence of low bioavailable sex hormones (due to high SHBG) and the bone-suppressive effect of rapamycin/under-nutrition. Despite optimal intake of calcium, vitamin D, Kā‚‚, and protein, his skeletal system appears to be in a ā€œcatabolicā€ state. High SHBG and low free testosterone/estradiol have left bone unprotected from resorption. Rapamycin and a low-insulin milieu (acarbose, vegan diet, potential caloric restriction) further tilt the balance by impairing osteoblast activity and reducing the normal post-meal pause in bone turnover. The result is an accelerated loss of bone density over two years.

Moreover, this is the summary of the reasons for my high SHBG:
In healthy men, vegetarian/vegan diets are consistently associated with higher SHBG. Mechanistic factors include lower protein and fat intake (which tend to increase SHBG) [Authorā€™s note: my diet is not low on protein or fat]. Caloric restriction and leanness raise SHBG via reduced insulin and IGF-1 signaling. Our patientā€™s use of rapamycin and acarbose mimics aspects of calorie restriction and high insulin sensitivity, again promoting SHBG elevation (acarbose has shown SHBG increases in hyperinsulinemic states. His high-normal testosterone is a compensatory response to the high SHBG, keeping free T just at the low end of normal. Normal thyroid and liver function rule out disease causes.

Rapamycin Effect on bones?
#2

Not sure about your question but Iā€™m sort of in a similar situation - very lean male in early 40s with mild osteopenia and T thatā€™s low but within the reference range. Recently I started on TRT. Havenā€™t had a follow up DEXA yet but hoping this starts to turn things around

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#3

FWIW, in the PEARL trial, rapamycin at 3mg/1-week in women after 48 weeks, resulted in superior muscoskeletal markers, the one notable effect in that trial, including I believe greater bone density (not 100% sure about the latter). There were no negative bone (or any other) effects reported. Now, those were fairly low doses, but there are papers out there claiming that rapamycin has a good effect on osteoporosis, and I posted some myself on this site, but of course there may be some diet or other confounders that might alter this dynamic. Anecdotally, my own experience of rapamycin effects is that the only positive impact seems to be superior muscle, joint and tendon recovery after exercise and definitely fewer aches and pains during exercise, increased exercise capacity and endurance. Itā€™s possible that all this is happening while my bones are becoming osteoporotic, but I doubt it. Of course my experience may not be applicable because first of all I donā€™t have comparative DEXA scans, donā€™t use acarbose and my diet is pescatarian.

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#4

Incase itā€™s helpful, Iā€™ll share my own experience that might demonstrate that rapa and acarbose doesnā€™t appear to negatively affect me.

Iā€™m also vegan and have the worldā€™s tiniest frame with osteoporosis in my family (mom broke a hip at 60). I was osteopenia at 40 (turned out my vit d was 10 and bone improved after supplementation). Iā€™m now 59.

2 years ago, I was barely in osteoporosis territory, and then last Nov, I was a little worse. I started taking Rapa in March of 24. I started acarbose last summer.

In Oct, I started talking calcium, and in Jan, I also started LDN (I mention the LDN because someone in the PEARL trail that Cronos Tempi mentioned was on both and saw bone improvement).

My dexa in May showed I gained a little bone back, and my hip is no longer osteo (one area was slightly worse but the other two areas showed improvement, but also a grain of salt because I was on a different machine). This year Iā€™m also working harder at resistance training.

Also, my second dexa used newer technology and also measured TBS which shows bone quality. My quality is good.

Oh, Iā€™m also taking taurine and Agetron swears that helps, too :).

Iā€™ve more recently started taking citrates because @John_Hemming said he believes there is a chance it might help over time.

Long way to say that on rapa and acarbose, we think I might have some improvement, and not a decline.

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#5

I think along with vitamin K-2 and calcium, you might consider daily tablespoon of taurine (in coffee you drink it). Buy it in bulk from Amazon Bulk supplements brand.

After 1 year of taurine my osteopenia T score returned to normal in lumbar and pelvis. I was on TRT for 2 years prior, so that only does so much for prevention.

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#6

Thanks for all the answers so far! The reason for my post was, on one hand, to share this that might have a connection to rapa, and on the other hand, to see if anyone else has had similar issues while using rapa or knows about some related studies. My plan is to conduct an experiment where I modify a few aspects of my lifestyle to see if it has an impact on SHBG and bone density. The challenge is that my lab work doesnā€™t really tell an obvious the SHBG is so high, so I just have to guess the causes. I will try to minimize my consumption of soy-based foods and increase my supplemental boron intake to 9mg per day (previously 3mg), although I suspect these changes wonā€™t have a significant impact. I will also stop taking acarbose and I am on the fence with rapa.

Edit: I am already taking 2.5g of taurine per day. Perhaps I up it to tablespoon per day then.

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#7

Why reduce soy? I thought it was an old wives tale that it affects hormones?

I love it as a vegan because itā€™s packed with protein.

#8

FWIW, some are worried about high protein leaching calcium out of bones, but not very likely on a vegan diet.

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#9

I also thought that soy doesnā€™t affect hormones, but the endocrinologist thought that it can be estrogenizing for men (estrogen raises SHBG). My understanding is that the evidence for that is weak at best, but since I donā€™t have strong alternative theories for the high SHBG, I figured it is worth to try to minimize my soy intake.

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#10

This is the first time Iā€™ve heard this, so thank you.

I do make an effort to get enough protein due to my diet, so do you know what is considered ā€˜highā€™ in this context ?

I donā€™t always get there, but in general, I aim for aprox 1.6 grams of protein per kg. Iā€™m following the guidance that vegans should eat a little extra protein due to the fiber making some of it less bioavailable and the slightly worse amino acid profile in plant based foods. But some people say this is not necessary, but I am puny and need all the muscle I can get!!!

Any thoughts?

#11

Impact of Dietary Protein on Osteoporosis Development

ā€œOsteoporosis is a frequent yet unsolved health problem among older people. The influence of dietary protein still raises many questions regarding its quality and quantity in the context of bone health. The aim of this manuscript is to review the latest evidence on plant and animal protein influences on bone health in various groups of patients. The review is based on original studies, meta-analyses, randomized controlled trials, and prospective cohort studies published in PubMed and Cochrane databases during the last five years. Combining plant and animal protein with physical activity has the best effect on bones (muscle strengthening and reducing the risk of falls), while high protein intake can have adverse effects during bed rest. Despite the content of isoflavones, plant protein is not more beneficial than animal protein (dairy products) and can increase bone resorption markers. Hypoestrogenism due to menopause or eating disorders leads to low bone density and an increased risk of osteoporosis. A well-balanced diet with sufficient energy supply and protein intake (both of plant and animal origins) and adequate physical activity are crucial to ensure bone health. Dietary interventions should consider the quantity and quality of protein in patients with other comorbidities, particularly in an aging society.ā€

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#12

The Supplement AlgaeCal Plus and Strontium Boost (both by at Algaecal.com) significantly improved my bone density. Iā€™m a lean male as well and on Rapamycin.

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#13

Beth,
Have you read about icariin having positive effects on osteoporosis?

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#14

Iā€™ve not heard about icariinā€¦ something new to google!!!

I may be back with follow up questions, and thank you for chiming in!

#15

Soy BLOCKS estrogen receptors, so, if anything, would decrease systemic estrogen. The molecular structure of soy is slightly different than estrogenā€¦

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#16

Nicari itā€™s great that a man your age even knows his bone density. Iā€™m near 72, broke my femur 5 years ago and have never been the same, so glad youā€™re on it. I listen to a Dr Doug podcast ( the Dr. Doug show) an orthopedic surgeon who quit to focus on bone health. Heā€™s very much against being vegan when it comes to bone health - I was formally vegan but he and others have scared me into adding some animal products, yogurt, eggs, turkey mostly. I am convinced full plant based is the best for ones overall health though, to say nothing of those poor animals. (How schizophrenic our society is when it comes to animals.) Anyway might want to check him out. He recently had a guy on who was praising Vit K4, taking 45mg a day, and that it is superior to K7, but a month or so later Dr. Doug had an issue with it which I canā€™t remember. Iā€™m taking 22.5mg of it daily now though, along with a cheaper algae calcium product, have heard itā€™s best coming from algae. I do get the algae cal brand of collagen though as it has some special ingredient. Good luck.

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#17

Thanks for the stronium reminder I ran out 3 months ago and never got more, I think because I read the stronium that has been studied is a different kind used in Europe, and safety/efficacy of what we take in the US is not settled, but Iā€™ve been taking it for years and donā€™t think itā€™s hurt but have no idea if itā€™s helped, but might as well keep taking it.

#18

Beth canā€™t remember the podcast she was on (has been several years) but her name is Dr. Kristi Funk, a breast cancer surgeon. (Operated on Sheryl Crowe and Angelina Jolie) and she one day, after reading all the research, came home and threw all the animal products out and her entire family (has 3 young boys I think) became vegan. She is an expert on soy and has no problem with it, something about the different receptors. Sheā€™s probably on other podcasts too if you want to check her out.

#20

Thank you @Candleflower !!! This is great to hear because it was just yesterday I entered my high protein soy milk in Cronometer and was floored to see that in only 2 lattes (1 cup of soy in each), I get a third of my protein needs and 85% of leucineā€¦ I had no idea the amino acid profile was THAT good!!

#21

I agree with this. Eat bones and cartilage and egg shells, add some lean animal products to your diet and lift much heavier. You need high mechanical tension to get the best benefit.