How Do You Formulate Your Risk/Benefit Equation for Taking Supplements?

I’m still new to this group but it looks like we have a pretty good age distribution, a high level of health awareness, and for many among us, rapamycin is but one among many supplements we take to improve our health and longevity.

Now in my 70s, I have been taking nutritional supplements since I was 24, adding and dropping supplements or changing doses along the way as the profile of evidence changed over the years. Those of you who were taking supplements around the time I started know how little good research there was to inform risk/benefit decisions.

Nonetheless, it was possible to find research that supported mostly rational decisions about whether to take a specific supplement. One of my informal decision rules at that time was to weigh downside risk much more heavily on upside benefit. I was not averse to taking a supplement for which the benefit was probable but as yet unproven, but I avoided supplements where the evidence of risk was stronger, irrespective of the benefits. (Of course, price and my budget figured in someplace.)

Now, some 50 years later, even though the number of supplements I take has expanded from a half dozen to five times that, my basic decision criteria have not changed substantially, with one exception. That exception is rapamycin. As a longevity drug, the list of probable benefits to someone my age is growing and they are significant. However, I’m not certain evidence for any of those probable benefits has crossed the line of generalized certainty based on large-n, multi-trait/multi-method (including randomized case control) evidence such as we have for many supplements. The risks of taking rapamycin, some of them at least, are clearer, albeit often derived from a different use of the drug. One somewhat theoretical risk I personally wonder about is if rapamycin might unfavorably tip a delicate balance of power between my immune system’s successful battle with a few nascent cancer cells of which I am unaware.

How do others formulate their risk/benefit decisions? Have you altered your general approach to making these decisions when it comes to taking rapamycin? I have changed my standards, I think, because the probable benefits seem more important to me at my age. If I were 25 years younger, I think I would be on the sidelines until we had at least a little more human evidence. Are others in our group still waiting and watching?

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Hi Rob, I’m 70 and like you have been interested in diet and health since I was young. I read Adele Davis ( Let’s Eat Right to Keep Fit (1954) and Let’s Get Well (1965)) when I was a teenager. I also was briefly on a Macrobiotic diet in high school because I wanted to be a Buddhist (deadly nightshade scared me). I still think of the Yin/Yang symbol when I think of the cycling of mTOR, on and off.
I’m also a long time supplement user, mine went from a couple to a whole bunch a couple of years ago. I’ve been fine tuning them and feel like my health is very good. But I’ve done a lot of reading, here and all over the internet, and decided to start rapamycin. I started taking Metformin 2 years ago because I thought that the preponderance of evidence showed that the risk/reward ratio was worth it. I take 850mg at night and feel no effects. I’m careful and am preparing to take a full battery of tests before (and after) starting rapamycin. I’ll start at a low dose (1mg/week) to start and then move up. I doubt I’ll ever go higher than 5-6 mg/week just because I tend to be conservative on dosing in general and my body seems sensitive. I’m hoping to see good results but from reading here it’s certainly possible that I won’t see any. But I think it’s worth a try.

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It’s a great question. To avoid the polypharmacy problem, I limit myself to 10 chemical interventions each week (with 1 day of zero chemicals each week). I don’t count food or dried food or spices / herbs or food powders (protein powder, moringa, wheatgerm, etc). If I find a new compelling chemical that I want to experiment with, I have to drop something from my list. I find that if I don’t have hard limits, I’ll slide back to the 30+ chemicals I was taking everyday previously.

Pharmaceuticals I pick to address issues with my blood markers (apoB, HbA1c are my targets). I go for drugs shown to also have longevity benefits. Aside from rapa I wouldn’t take a pharmaceutical just because it extended the lifespan of a mouse. And for supplements, I mostly think they don’t do much so missing out on “a great one” because I limit myself won’t matter compared to lifestyle factors.

Good luck

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Excellent questions. I view longevity as a marathon with hurdles or obstacles (like arteriosclerosis, dementia, diabetes, cancer, inflammation, etc…). Any medication or supplement that can help me clear a hurdle or obstacle gets added to my stack. For instance, all of the data from Rapamycin leads me to believe it helps with almost all obstacles so I added it. Based on my blood tests, I need a little help with my LDL and ApoB, so I added Bempedoic Acide + Ezetimibe. My HBA1C was trending higher so I added Metformin which is also synergistic with Rapamycin. I wanted to prevent cognitive decline and dementia, so I added Lithium Orotate, etc…

If there is a strong detriment or side effect, then that medication or supplement gets removed. For instance, I took Rosuvastatin (5 mg) for a few days and developed intense muscle soreness. I tried EOD, but no luck. Finally, I gave up after 2 weeks.

I hope this helps…

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This is a great discussion and a reminder of the strength of our small community. Even though our paths differ, the sharing feels good. Thank you @ng0rge, @Joseph_Lavelle, @DeStrider.

I still recall reading every one of the Adele Davis books. She was one of the very few pioneers who sought to develop an integrated perspective on nutrition and health. I also recall how the medical community and popular press considered her early death proof that her views were worthless. That was an early insight into their limitations. I’ll share others when time permits.

The problem of supplement overload, polypharmacy, liver health, etc. is always on my mind. I don’t have as much of a solution as a strategy. I classify my supplements for potential risk, potential benefit (all based on empirical research favoring quality research), degree of concentration, and a few other variables such as how closely they are related to my weak areas. As for concentration, my concern is low for supplements such as my daily dose of 5 mg. L-Ergothioneine which I could obtain in my diet. I review these at least annually based on current research. I review higher concentration supplements – such as concentrated curcumin, metformin, or ezetimibe – at least twice yearly to see if their inclusion remains justified. At present, rapamycin is the only “supplement” that I re-consider with each alternate week dose. Most weeks, I take at least one day off from most supplements.

While I take some supplements as research-based articles of faith, I have been able to get hard metrics on the benefits of other supplements. Astaxanthin is an example. My hsCRP has never been above 3.0 in the 15 years I have measured it but, through diet, I was able to reduce it to a consistent range between 0.5 and 0.9. After that, a research paper convinced me to add astaxanthin to my supplement stack to see if I could lower it further. I did and my level is now consistently less than 0.3. A good place to stop, I think.

Even though some research suggests little benefit at my age, my current goals are to lower my Apo(b) and my SHBG in ways (for Apo(b)) that do not involve statins. I tried them and cannot put up with the muscle pain and dysfunction. I also have genetically low LDH that runs 15-20% below the lower acceptable boundary and has for decades. For some, these low levels causes muscle pain or weakness but it has not for me. I ran 10Ks and marathons for four decades with no weakness or pain and generally placed near the top of my age division. I’m not optimistic about reducing or eliminating this deficiency.

I fully accept that the relevant efficacy of my supplement mix could range from slightly negative to significantly positive and that a few supplements might be a complete waste of money. Such is the risk of this kind of approach and I try to remember that in evaluation science, the last question to be asked and answered is, “Compared to what?”

I’m happy to share further if anyone has questions about my stack or has suggestions to share related to my current goals.

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@RobTuck If you’d like, you can share your stack here and open it up for constructive comments. It’s always good to look at what others are doing. There’s a topic all about What is your supplement stack.

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That is good to hear. Can you share more on what dose, how long did you take it for CRP to come down? Was anything else involved that could have drifted the effect instead? Did you test with

SHBG

This one may actually not be bad to have on the high side. It might be an example of healthspan perhaps suggesting low is better, but longevity suggesting that high actually is better.

There is one thread on this where I shared a lot of papers and reasons for such a read.

(It’s a bit similar to how higher testosterone, mTOR, Growth Hormone/IGF-1, protein intake, etc might be pro short/medium term healthspan but not pro long term healthspan/maximal longevity).

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@Neo ,

Thank you for the tip on SHBG. I’ll follow up and hope for a brighter outlook.

On Astaxanthin, as is usually the case with these N=1 inferences, it is not possible to be certain. What I am reasonably certain of is that my supplement regimen did not change in ways that might explain the effect over the period of interest. I usually obtain a comprehensive panel once or twice a year. Prior to initiating astaxanthin, I had hsCRP readings in the 0.9-0.5 range. My next reading, about a year later, was 0.29. Part of this period spanned Covid where I minimized testing, which might further reduce confidence. If you decide to try astaxanthin, I recommend the natural form (Bio-astin is good and Costco puts it on sale periodically – right now I think). The profile on the synthetic form is different.

Most of that time my dose was 12 mg. but for awhile I was taking 18 mg. Another unfortunate variable.

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