Side Effects of my Longevity Protocol

In this article, I´ll briefly discuss some roadblocks and side effects I have encountered from experimenting with healthspan interventions.

Liver and kidneys

Is all of the stuff I do and take bad for my liver and kidneys? My levels of cystatin C have improved and ALT/AST are always well within the normal range (both below 25 U/l). The only thing that consistently spiked my liver enzymes was acarbose.

Drug side effects

Metformin: Initially, I could not function due to fatigue, which went away after one to two months of use. However, the bloating and indigestion did not.

SGLT-2 inhibitors: I had to pee a lot. Furthermore, I was constantly dehydrated, which was the reason I stopped taking them. I discuss my experience with metformin and SGLT-2 inhibitors in more detail here.

Semaglutide: I had some slight morning nausea for the first couple of weeks. Furthermore, I lost some of the “pleasure” associated with eating (which though, for me, is not an unwanted effect). I discuss my experience with semaglutide in more detail here.

Senolytics: Flu-like symptoms & diarrhea on the first and second day. Dexibuprofen helped somewhat. I discuss my experience with senolytics in more detail here.

Rapamycin: Initially some canker sores, and pitting edema in my legs. Also, for the first few months, my fasting blood sugar was elevated (100-120mg/dl). I discuss my experience with rapamycin in more detail here.

Knee pain

I did have one potentially major adverse effect, which could have been due to high-dose rapamycin during my first year on it (10mg/w). After 6 months or so, I started to get some knee pain in both of my knees. However, I had started doing regular sprints at the same time I had started rapamycin, so it was impossible to say whether the rapamycin caused (or at least exacerbated) it.

Nonetheless, the knee pain could have been related to rapamycin’s inhibitory effect on tissue repair and anabolism (its negative effects on wound healing are well-known). While the knee pain did not get worse for many months, it also did not go away completely until I had stopped taking the rapamycin for three months. An MRI scan revealed no signs of pathology.

It could have been a form of patellofemoral syndrome (runners’ knee), or it could have been something else. I do not know, and probably never will. Because of this, I decreased my rapamycin dose from 10mg to 5mg and now I also incorporate a 1-2 month break every year.

If the knee pain was indeed caused by rapamycin and if it did not have gone away (which it fortunately did), then this single side effect (i.e., developing degenerative knee changes for a long time to come) would have canceled out all of the potential benefits of rapamycin (and perhaps even all of the rest) because a potential inability to properly exercise would do a lot of damage to my body overall.

Every time I have talked to doctors and longevity scientists, I realized that a lot of what longevity medicine does is far from established by “hard” science. Even though there is a vast amount of theoretical knowledge on the subject, when it comes to evaluating objectively how my interventions are performing, there are few to no useful ways to test for it.

Even though I track a long list of blood markers, body composition via DEXA, metabolic health via CGM, and do a full-body MRI every couple of years, I have little to no clue whether my interventions are actually doing something, or even worse, whether they are doing more harm than good.

What complicates the problem is the impossibility of getting truly objective markers. For example, I recently tested for FGF23. Because the marker was included in two different panels, by mistake, I tested for it twice within a 10-minute period. The delta between the two blood draws was quite large (39pg/ml vs. 50pg/ml on a reference range of 32-95pg/ml), despite both samples having been taken literally simultaneously and despite both having used the same assay.

Unfortunately, most of the objective data available is not only corrupted by biological and laboratory fluctuations but assays from one company to the next are also not comparable to one another. And neither are individuals.

All this leaves me with the following problem:

When it comes to evaluating the effects on biological age, I have little idea what to truly test for. Every method available to date (e.g., telomere length, Howarth clock, glycan score) has severe limitations. For example, a multi-day fast is known to set back the Howarth clock by multiple years. Or excessive exercise is known to increase glycan age by increasing levels of tissue inflammation.

Blood markers have a lot of problems. Individuals vastly differ from one another, in part due to genetic and endocrine differences, which then influence laboratory parameters in ways unrelated to underlying health status. Furthermore, essays between different companies differ. These issues make it hard to impossible to compare myself to other individuals, and at times also to compare myself to myself.

In sum, I am flying blind.

Cost, effort, risks, benefits, “why”

I discuss cost, effort, how all of this started, whether I am worried about long-term consequences, benefits, risks, side effects, and why I do everything I do, here.

My Longevity Protocol (Long & Technical Version)

This article is part of a much larger post describing my complete longevity blueprint. For my full protocol, read here.

Longevity Protocols

Disclaimer

The content on this website represents the opinion and personal experience of the author and does not constitute medical advice. The author does not endorse the use of supplements, pharmaceutical drugs, or hormones without a doctor’s supervision. The content presented is exclusively for informational and entertainment purposes. Never disregard professional medical advice or delay in seeking it because of something you have read on the internet.